Neutrophils are a type of white blood cell that play a significant role in the immune system of horses. They are involved in the body's defense mechanisms against infections and are typically one of the first responders to microbial invasion or tissue damage. Neutrophils function by engulfing and destroying pathogens through processes such as phagocytosis and the release of antimicrobial substances. In horses, the number and activity of neutrophils can be indicative of immune status and are often assessed in the context of infectious diseases, inflammation, and other health conditions. This page compiles peer-reviewed research studies and scholarly articles that explore the function, regulation, and clinical implications of neutrophils in equine health.
Hendrikx AL, Vendrig JC, Gehring R, van den Boom R, van Alphen J, Vernooij JCM, Teske E, Roelfsema E.To determine the effect of repeated IV administration of dexamethasone (0.06 mg/kg, q 24 h, twice) on WBC parameters in healthy adult horses. Unassigned: This prospective, longitudinal study was conducted from October 7 through November 5, 2024. Five warmblood mares received an IV dexamethasone sodium phosphate injection (DMI) at 0 and 24 hours and an IV injection with 0.9% sodium chloride solution at 48 and 72 hours. Blood samples were collected at 0, 6, 12, 24, 30, 36, 48, 72, 96, and 168 hours, and WBC parameters were evaluated using linear mixed-effects models. Unassigned: Leukocyte count,...
Samuels AN, Collins N, Albrecht M, Cuming R, Reed S, Gomez D, Toribio R.To evaluate associations between the neutrophil-to-lymphocyte ratio (NLR), nonsurvival, illness severity, and infectious etiologies. Unassigned: This was a retrospective multicenter study that included 100 healthy horses and 444 horses presenting with acute diarrhea to 5 equine referral hospitals. Inclusion criteria were diarrhea duration < 48 hours, complete hemograms, and outcome data. Illness severity was assessed using systemic inflammatory response syndrome. The results of pathogen testing for Salmonella spp, equine coronavirus, Clostridium spp, and Neorickettsia risticii/findlayensis ...
Santos R, Hunyadi L, Sundman E, Morales Luna L, Hyde SC, Cain M, Migl K, Ancira J, Tipton C, Rosa F.Severe equine asthma (SEA) is a chronic inflammation of airways affecting ~14-20% of adult horses in the Northern Hemisphere. SEA is characterized by a mixed phenotype of T helper cell responses with marked neutrophilia in the bronchoalveolar lavage fluid (BALF) of affected horses. Human studies have demonstrated the impact of gut microbiota in many diseases, including asthma susceptibility and severity. However, the potential role of the gut-lung axis in the development and persistence of SEA remains to be determined. This study aimed to identify key bacterial, archaeal, and fungal microbiota...
Eskandari G, Ahmadi Sheikhsarmast S, Ghasemi S, Mohri M.Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein involved in immune responses and inflammation, with established diagnostic utility in acute kidney injury (AKI) and systemic diseases. However, reference values for NGAL in healthy horses, particularly the Turkmen breed, remain poorly defined. Objective: This study aimed to establish reference values for serum NGAL concentrations in healthy Turkmen horses and to evaluate the influence of age, sex, pregnancy status and physical activity on its levels, as well as its correlations with haematological and serum biochemical variabl...
Cooper BL, Hobbs KJ, Bayless R, Stinson-Miller A, Gruber E, Hepworth-Warren K, Lavoie JP, Sheats MK.Severe equine asthma (sEA) is characterized by increased lower airway neutrophils that contribute to dysregulated inflammation through the release of cytokines, reactive oxygen species and neutrophil extracellular traps (NETs). NETs are composed of cell-free DNA (cfDNA) intercalated with enzymatic proteins and are known to be increased in the lower airway of asthmatic horses. The objectives of this study were two-fold: 1. Determine if cfDNA can be accurately measured in equine bronchoalveolar lavage fluid (BALF) and tracheal wash (TW) with a Qubit 4 fluorometer. 2. Determine whether Qubit-meas...
Zamith Cunha R, Gobbo F, Morini M, Salamanca G, Zanoni A, Bernardini C, Gramenzi A, Chiocchetti R.Evidence suggests that the endocannabinoid system (ECS) is crucial for regulating inflammation, cell proliferation and pain. The ECS is composed of cannabinoid receptors such as type 1 (CBR1), type 2 (CBR2) and GPR55, endocannabinoids and enzymes. Proteins of ECS have previously been localized in the epidermal cells of the horse hooves. Given the physio-pathological role and cellular distribution of the ECS across species, the authors hypothesized that cannabinoid receptors are expressed within the inflammatory cells, fibroblasts and endothelial cells of the equine hoof laminae, going beyond t...
Da Silva-Álvarez E, Martín-Cano FE, Alonso JM, Becerro-Rey L, Zabalo-Palomo C, Gil MC, Peña FJ, Ortega-Ferrusola C.This study aims to characterize and compare the uterine fluid proteome and cytokine profile of reproductively healthy mares (HM; n = 15) and mares with Streptococcus equi subsp. zooepidemicus (S. zooepidemicus)-associated endometritis (SAE; n = 9). Uterine flush samples collected during the follicular phase were analyzed by shotgun proteomics and multiplex cytokine assays. Equine proteins were mapped to human orthologs, and enrichment and network analyses were performed using g:Profiler, Metascape, ToppGene, and STRING/MCODE. SAE mares showed higher levels of IL-1α, IL-1β, GRO, IL12p...
Salinas-Varas C, Espinosa G, Muñoz-Caro T, Conejeros I, Gärtner U, Fey K, Arnhold S, Taubert A, Hermosilla C.Neutrophil extracellular trap (NET) are thin and long web-like structures composed of DNA and antimicrobial proteins released by activated polymorphonuclear neutrophils (PMN) as part of the innate immune response. Adipose-derived stem cells (ADSCs) represent an accessible, abundant and minimal invasive source of mesenchymal stem cells (MSCs), with high regenerative potential, immunomodulatory and anti-inflammatory properties. Although recognized immunomodulatory properties of ADSCs, their interaction with PMN and their role on NET formation remains poorly characterized. The present study aimed...
Sprenzel CJ, Amann B, Deeg CA, Degroote RL.Glycosylation of surface proteins is a crucial post-translational modification that reflects the activation status of neutrophils, the predominant leukocyte subset in humans and horses. Neutrophils have emerged as active contributors to diseases mediated by the adaptive immune system, such as equine recurrent uveitis (ERU), a sight-threatening disease in horses and a unique model for studying the pathogenesis of autoimmune uveitis in humans. Since changes in surface glycosylation can impact neutrophil function, we were interested in the surface glycosylation landscape on neutrophils from healt...
Meiseberg LK, Mergani A, Delarocque J, Imker R, Köhn D, Wanes D, Bonilla MC, Veldhuizen EJA, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N.Equine asthma (EA) is the most prevalent chronic lung disease in horses. Neutrophils are the main effector cells in severe EA. Neutrophil extracellular traps (NETs) have been described as contributors to severity in human asthma and chronic obstructive pulmonary disease. Thus, we aimed to investigate if NET-related factors in equine neutrophils, blood and bronchoalveolar lavage fluid (BALF) allow us to differentiate EA severities and to identify NET-related mechanistic insights in EA. We quantified NETs and NET-related factors in the blood and BALF of eight healthy horses and 18 horses with di...
Pınar O, Çelik Doğan C, Aktaran Bala D, Kumaş C, Mete A.Riding clubs face significant financial losses due to upper respiratory infections caused by Beta-hemolytic (β-hemolytic) streptococci, leading to strangles and related diseases that negatively impact the health and performance of horses. Our objective was to determine the relationship between these inflammatory cells, the presence of β-hemolytic streptococcal species, and the clinical symptoms exhibited by the horses. This study investigated the presence of β-hemolytic streptococcus in 133 tracheal lavage samples from horses exhibiting various clinical respiratory symptoms and quantified t...
Urayama S, Muko R, Muranaka M, Mita H, Ohta M, Matsuda H, Tanaka A.Systemic inflammatory response syndrome (SIRS) induced by endotoxemia is usually secondary to colitis and is a major cause of high morbidity and mortality in horses. Non-steroidal anti-inflammatory drugs (NSAIDs), such as flunixin meglumine (FM) and meloxicam (MX), are used to improve clinical outcomes in SIRS/endotoxemia. These NSAIDs suppress tumor necrosis factor-alpha (TNF-α) levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the inhibitory effects of FM and MX on TNF-α in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear ce...
Raïsky C, Vives BM, Leduc L, Symoens A, Tavanaeimanesh H, Richard H, Juette T, Bédard C, Leclère M.Steaming hay reduces respirable particles and is commonly used to feed horses with asthma. However, it showed inconsistent benefits in clinical studies. Objective: (1) To assess the effects of steamed hay on lung function and airway inflammation in horses with severe equine asthma (SEA) in remission; (2) To compare these effects with a dry hay diet. Methods: Cross-over in vivo experiment. Methods: Horses were fed steamed and dry hay for 4 weeks in a prospective, cross-over study, with a 4-week washout period. Lung function, bronchoalveolar lavage (BALF) cytology, and a 23-point weighted clin...
Bozzola C, Sala G, Stancari G, Ferrucci F, Zucca E.Exercise-Induced Pulmonary Hemorrhage (EIPH) results from alveolar capillary stress failure after strenuous exercise, leading to bleeding and pulmonary inflammation. Bronchoalveolar lavage fluid (BALF) cytology is considered the gold standard for the assessment of airway inflammation; however, it is often considered more invasive compared to tracheal wash (TW). It has been demonstrated that TW is a reliable diagnostic tool that may substitute BALF to diagnose and grade the severity of EIPH in racehorses; however, no information about airway inflammation in EIPH-affected horses has been reporte...
Migliorisi A, Nottle B, Smanik LE, Nout-Lomas YS, Hassel DM.To (1) compare total nucleated cell count (TNCC) and neutrophil-to-lymphocyte ratio (NLR) at admission between horses with medically managed, large intestinal (LI) and small intestinal (SI) surgical colic; (2) compare TNCC and NLR between survivors and nonsurvivors; and (3) investigate associations between TNCC, NLR, surgical intervention, and outcome. Methods: Case-control study. Methods: Single, academic institution. Methods: A total of 341 adult horses diagnosed with noninfectious medical or surgical colic. Results: Admission TNCC did not differ between the medical and combined surgical gro...
Alves-Junior CDB, Ferreira TC, Nunes-Pinheiro DCS.This study evaluated the dynamics of blood immune-inflammatory biomarkers in response to exercise-induced changes in jumping horses. Methods: For this purpose, adult Brazilian Sport Horses (n = 9), aged 10.1 years, both sexes, underwent a specific training test consisting of warm-up, flatwork, and jumping exercises, and recovery on a 900 m sand track over 40 min. Clinical examinations and blood collections were performed at three time points: before (T0), immediately after (T1), and 1 h after (T2) the final exercise. Hematologic and biochemical parameters, such as total protein, gl...
Dörner C, Lagos N, Oyaneder L, Menarim BC, Ramírez-Toloza G.Osteoarthritis (OA) is an inflammatory joint disease and the leading cause of musculoskeletal disability affecting human and veterinary patients. New therapeutics halting inflammation while preserving joint homeostasis remain a critical need. Voltage-gated sodium (NaV) channels regulate the pro-inflammatory response of macrophages in the synovium, the central driver of joint homeostasis. Neosaxitoxin (NeoSTX) is a phycotoxin that blocks NaV channels, conferring a unique potential to regulate joint inflammation. This study evaluated the safety of intra-articular administration of NeoSTX in hors...
Lendl L, Wirth C, Merle R, Barton AK.Mild-moderate equine asthma (MEA) is a very common but underdiagnosed pulmonary disease in horses, with mild cases not showing clinical respiratory signs. This study evaluates the influence of a standardized lunging exercise test (SLET) on bronchoalveolar lavage fluid (BALF) cytology in MEA horses. We hypothesized that SLET would increase the total nucleated cell count (TNCC) and/or percentages of inflammatory cells associated with EA. In a prospective, randomized, non-blinded, between-subjects study design of two independent groups, 39 horses (17 mild and 22 moderate) were included. They were...
Hobbs KJ, Ueda Y, Le Sueur ANV, Cooper BL, Burke MJ, Sheats MK.To determine the effect of hemoperfusion with a polymer-based column on systemic cytokine concentrations and neutrophil dysfunction in lipopolysaccharide-treated horses in vivo. Unassigned: 6 university-owned horses received 60 ng/kg lipopolysaccharide, IV, as a bolus and then 60 ng/kg, IV, as a constant rate infusion over 1 hour. Endotoxemia was confirmed by clinical signs and neutropenia. In a crossover model that was completed from January 2024 through July 2024, hemoperfusion was performed for 4 hours with either a sham or polymer column. Blood was collected at 5 time points over a 72-hour...
Drespling J, Berwanger L, Kühn H, Schwarz B, Doherr M, Mundhenk L.Mucus parameters are hallmark diagnostic features of equine asthma (EA). Objective: To investigate the relationship between mucus quantity score and mucus viscosity score with signalment, history, clinical findings and cytological parameters. Methods: Retrospective cross-sectional study. Methods: Mucus quantity and viscosity scores, signalment, history and clinical findings recorded for diagnostic purposes from up to 1599 samples, and cytological values of the corresponding bronchoalveolar lavage fluid (BALF) and tracheobronchial secretions were analysed. The cut-off value of a mucus quantity ...
Albornoz A, Morales B, Fernandez VB, Henriquez C, Quiroga J, Alarcón P, Moran G, Burgos RA.Equine asthma is a chronic respiratory disease characterised by neutrophilic inflammation, airway hyperresponsiveness, and impaired pulmonary function. Obesity, increasingly prevalent among domestic horses, has been identified as a potential risk factor for exacerbating inflammatory conditions. This study aimed to explore whether obesity modifies neutrophil metabolism and inflammatory responses in horses affected by asthma. Six asthmatic horses in clinical remission were categorised into two groups: obese and non-obese, based on body condition score. Serum levels of interleukin-1β (IL-1β) an...
Alves LSS, Hasuda AL, Giordano LGP, Frederico I, Dos Santos IH, Pereira PFV, Lisbôa JAN, Flaiban KKMDC.This study investigated isolation of equine neutrophils and the assessment of their antioxidant function using the nitroblue tetrazolium (NBT) reduction test, an indicator of reactive oxygen species (ROS) activation. The objective was to test the viability of neutrophils isolated from equine whole blood and their ability to undergo respiratory burst, comparing the results with whole blood. The hypothesis tested was that isolation of equine neutrophils allows for effective functional evaluation, even after isolation process, with no significant differences between whole blood and isolated cells...
Lection J, Schnobrich M, Wagner B, Byron M, Back B, Rollins A, Castro Alves RF, Cheong SH, Diel de Amorim M.To evaluate inflammatory cytokine and chemokine concentrations in endometrial samples collected by cytobrush or swab as a potential screening diagnostic marker for equine endometritis. Unassigned: 88 mares had endometrial samples collected, which included cytobrush, swab, and/or biopsy. Clinical reproductive records, reproductive ultrasound examination, endometrial cytology and culture results, and biopsy grading score were recorded. Fluorescent bead-based multiplex assays for the inflammatory markers interferon-γ, interferon-α, IL-1β, IL-4, IL-10, IL-17A, soluble CD14, tumor necrosis facto...
da Silveira BP, Kahn SK, Legere RM, Bray JM, Cole-Pfeiffer HM, Golding MC, Cohen ND, Bordin AI.Using a horse foal model, we show that enteral immunization of newborn foals with Rhodococcus equi overcomes neonatal vaccination challenges by reprogramming innate immune responses, inducing R. equi-specific adaptive humoral and cell-mediated immune responses and protecting foals against experimental pneumonia challenge. Foals were immunized twice via gavage of R. equi (immunized group) or saline (control group) at ages 1 and 3 days. At age 28 days, all foals were challenged intrabronchially with R. equi. Post-challenge, all 5 immunized foals remained healthy, whereas 67% (4/6) of control foa...
The objective of the present study was to investigate the influence of daily rhythms on the immune and inflammatory systems in horses, considering white blood cell count (WBCs), leukocyte subpopulations (neutrophils, basophils, eosinophils, lymphocytes, and monocytes), CD4+, and CD8+ lymphocyte populations, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Ten Italian Saddle horses (7-12 years old, body weight 480 ± 30 kg) underwent blood sampling every 4 h over a 24-h period. The COSINOR method was used to identify rhythms and their parameters. A one-way ...
Labens R, Saba C, Williams J, Hollis A, Ensink J, José-Cunilleras ELV, Jordana-Garcia M, Bergvall K, Ruppin M, Condon F, Spelta C, Elce Y....Intralesional chemotherapeutic administration represents an important treatment option for equine cutaneous neoplasia. Tigilanol-tiglate (TT), a novel molecule extracted from Fontainea picrosperma, an Australian rainforest plant, is registered for intratumoural treatment of canine MCT, leading to rapid oncosis and tumour slough. Evidence from horses is limited but suggests that efficacy may be similar. Objective: To evaluate the response to intratumoural TT treatment in horses with sarcoids (fibroblastic/nodular) and cutaneous melanomas. Methods: Two noncontrolled prospective multicentre clini...
Conley HE, Davis KU, Adler KB, Lavoie JP, Sheats MK.Asthma is a chronic inflammatory airway disease that affects millions of people worldwide. Horses develop asthma spontaneously and serve as a relevant model for multiple phenotypes and endotypes of human asthma. In horses with equine asthma (EA), environmental organic dust triggers increased inflammatory cytokines, excess airway mucus, reversible bronchoconstriction, and airway inflammation. In horses with severe EA (sEA), lower airway inflammation is invariably neutrophilic, making sEA a potential model for severe neutrophilic asthma in humans. Alveolar macrophages (AM) and airway neutrophils...
Mason SJ, O'Neill HD, Bladon BM.The objective was to investigate synovial sample appearance, total nucleated cell count (TNCC), total protein concentration (TP), and neutrophil percentage in horses with acute articular fractures to aid decision making in acutely lame horses. Methods: Retrospective case series. Methods: Synovial fluid samples (n = 55). Methods: Synovial fluid records were analyzed over an 11 year period from horses undergoing lag screw fixation or arthroscopic fragment removal of intra-articular fractures within 48 h of occurrence. Horses were excluded when presented with wounds close to the joint or ...
Wilkins PA, Wong D, Slovis NM, Collins N, Barr BS, MacKenzie C, De Solis CN, Castagnetti C, Mariella J, Burns T, Perkins G, Delvescovo B, Sanchez LC....Sepsis has been defined in humans as the concurrent proven or suspected presence of microbial infection and the systemic inflammatory response syndrome (SIRS). Sepsis is the leading cause of morbidity and mortality in neonatal foals. The clinical utility of using SIRS or its individual components to predict infection and mortality in critically ill foals is currently unknown. Objective: Assess the ability of history and signalment, clinical findings, laboratory results, and SIRS-related indices to predict infection and mortality in critically ill foals. Methods: Retrospective, multi-center, cr...
Hansen S, Otten ND, Ceron JJ, González-Arostegui LG, Peres-Rubio C.The contribution of redox imbalance to equine asthma (EA) pathogenesis remains unclear. Objective: (1) validate and measure a panel of redox biomarkers in the tracheal wash (TW) and bronchoalveolar lavage (BAL) samples from horses with neutrophilic and mastocytic mild-moderate EA (MEA) and severe EA. (2) Evaluate the same panel in saliva and serum for comparative purposes. Methods: A total of 117 horses: 37 healthy, 26 mastocytic MEA, 29 neutrophilic MEA, and 25 severe EA. Methods: Cross-sectional study using TW, BAL, and serum and saliva sampling. After assay validation, redox biomarkers-ferr...
Hiemstra PS, Maassen RJ, Stolk J, Heinzel-Wieland R, Steffens GJ, Dijkman JH.Antileukoprotease (ALP), or secretory leukocyte proteinase inhibitor, is an endogenous inhibitor of serine proteinases that is present in various external secretions. ALP, one of the major inhibitors of serine proteinases present in the human lung, is a potent reversible inhibitor of elastase and, to a lesser extent, of cathepsin G. In equine neutrophils, an antimicrobial polypeptide that has some of the characteristics of ALP has been identified (M. A. Couto, S. S. L. Harwig, J. S. Cullor, J. P. Hughes, and R. I. Lehrer, Infect. Immun. 60:5042-5047, 1992). This report, together with the catio...
Bullone M, Lavoie JP.Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, while experiments in which the disease is artificially induced have helped discovering biological and molecular pathways leading to allergic airway inflammation, their contribution to the understanding of the causality of the disease has been more limited. Horses naturally suffer from an asthma-like condition called "heaves" which presents sticking similarities with human asthma. It is characterized by reversible airway obstruction, airway neutrophilic inflammation, an...
Hahn S, Giaglis S, Hoesli I, Hasler P.The intention of this review is to provide an overview of the potential role of neutrophil extracellular traps (NETs) in mammalian reproduction. Neutrophil NETs appear to be involved in various stages of the reproductive cycle, starting with fertility and possibly ending with fetal loss. The first suggestion that NETs may play a role in pregnancy-related disorders was in preeclampsia, where vast numbers were detected in the intervillous space of affected placentae. The induction of NETosis involved an auto-inflammatory component, mediated by the increased release of placental micro-debris in p...
Cross AR, Higson FK, Jones OT, Harper AM, Segal AW.1. The absorption coefficient of human neutrophil plasma-membrane reduced-minus-oxidized cytochrome b-245 was determined [delta epsilon (mM; 559-540 nm) = 21.6 cm-1]. 2. Neutrophil polymorphonuclear leucocytes (neutrophils) were prepared from human, ox, horse and pig blood. In each case plasma-membrane fractions were found to contain low-potential cytochrome b. When membranes from horse neutrophils were incubated anaerobically with either NADH or NADPH the cytochrome b became reduced. Prior stimulation of the cells with phorbol myristate acetate did not increase the rate or extent of cytochrom...
Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP.Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway. Six neutrophilic severe asthmatic horses and six healthy controls were studied while being treated...
Pirie RS.Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity-mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fu...
Ivester KM, Couëtil LL, Moore GE.Mild equine asthma is presumed to arise in response to environmental exposures but the relative impact of differing inflammatory phenotypes upon performance are largely unexplored. Objective: Airway inflammation negatively affects performance and cytological phenotype varies with environmental exposure. Methods: Thoroughbred racehorses in active training and racing. Methods: Thoroughbreds were recruited 24-48 hours before racing. Each horse was eligible for re-enrollment with each race entry. Within one hour of race completion, physical examination, respiratory endoscopy, and BAL were performe...
Holcombe SJ, Jackson C, Gerber V, Jefcoat A, Berney C, Eberhardt S, Robinson NE.We examined the effect of stabling on upper and lower airway inflammation in 14 yearling Arabian horses that had been at pasture since birth. Horses were divided into 2 groups of 7. One group was stabled for 3 months and the other remained at pasture. The groups were then switched over for another 3 months. The nasopharynx, guttural pouches and trachea were examined endoscopically and bronchoalveolar lavage performed every month. An upper airway inflammation score was devised based on the magnitude of pharyngeal lymphoid hyperplasia and guttural pouch inflammation. During stabling this score r...
Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA.Heaves in horses shares many similarities with human asthma, including lower airway inflammation, reversible airway obstruction, and bronchial hyperresponsiveness. Extrinsic asthma is an allergic response to environmental allergens and a similar immunologic mechanism may be implicated in heaves. It is now recognized that a Th2 subset of CD4+ lymphocytes is associated with allergic diseases such as atopic asthma. The purpose of this study was to determine whether airway inflammation in heaves is associated with a pattern of expression of cytokine suggestive of a Th2 type response. The expressio...
Bedenice D, Mazan MR, Hoffman AM.The objective of this study was to examine the relationship between chronic cough, pulmonary mechanical function, bronchial hyper-responsiveness, and peripheral airway inflammation in adult performance horses with nonseptic inflammatory airway disease (IAD). Objective: We hypothesized that horses with a presenting complaint of cough have a higher percentage of inflammatory cells on bronchoalveolar lavage (BAL), greater airway obstruction, and airway hyper-responsiveness (AHR) than do horses without cough. ANIMALS/SAMPLE POPULATION: Adult performance horses (n = 137) referred for evaluation of ...
Ainsworth DM, Grünig G, Matychak MB, Young J, Wagner B, Erb HN, Antczak DF.In horses prone to developing recurrent airway obstruction (RAO), we tested the hypotheses that the cytokine profile in the bronchoalveolar lavage (BAL) cells of affected horses would reflect a polarized Th-2 response; that cytokine and chemokine alterations would occur within 24 h of allergen exposure; and that allergen exposure would induce alterations in the expression of the transcription factor t-bet (t-box-expressed in T-cells). The expression levels of interleukin-4 (IL-4), IL-13, Interferon-gamma (IFN-gamma), t-bet, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) wer...
Sheats MK.The most recent definition of sepsis in human medicine can be summarized as organ dysfunction caused by a dysregulated host response to infection. In equine medicine, although no consensus definition is available, sepsis is commonly described as a dysregulated host systemic inflammatory response to infection. Defense against host infection is the primary role of innate immune cells known as neutrophils. Neutrophils also contribute to host injury during sepsis, making them important potential targets for sepsis prevention, diagnosis, and treatment. This review will present both historical and u...
Couëtil LL, Rosenthal FS, DeNicola DB, Chilcoat CD.To evaluate the association among clinical signs, results of cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and measures of pulmonary function in horses with inflammatory respiratory disease. Methods: 9 healthy horses, 5 horses with inflammatory airway disease (IAD), and 9 horses with chronic obstructive pulmonary disease (COPD). Methods: Clinical examination, lung function tests, and BAL were performed on each horse. Results: Standard lung mechanics of horses with exacerbated COPD differed significantly from those of healthy horses; however, there were few differences among horse...
Chang MH, Kim KH, Kim HS, Jun HJ, Kim DH, Jang JH, Kim K, Jung CW.Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine (CSA) is standard therapy in patients with severe aplastic anemia (SAA) who do not have an available HLA-matched sibling donor. Methods: The current study aimed to determine the predictive factors for response to IST in patients with SAA and to identify prognostic factors following IST. A total of 62 patients diagnosed with SAA who received IST with either rabbit ATG (n = 33) or horse ATG (n = 29) plus CSA between October 1994 and December 2007 were included. Results: With a median follow-up duration of 60.5 mo...
Kotilainen T, Huhtinen M, Katila T.The objective of this study was to investigate the inflammatory reaction induced in the equine uterus by insemination with fresh and frozen semen. Eleven groups (6 to 8 mares per group) were studied during 2 breeding seasons. The mares were inseminated using raw semen, frozen semen, extended fresh and frozen semen, concentrated fresh semen, seminal plasma and seminal extenders only. One group was bred naturally. Six hours after insemination, the uteri were flushed with 50 ml of phosphate-buffered saline (PBS). Seventeen out of 104 samples (16%) exhibited slight bacterial growth. Neutrophil con...
Beekman L, Tohver T, Léguillette R.The pathophysiology of inflammatory airway disease (IAD) is unknown, but in some cases involves the accumulation of mast cells, neutrophils, or both in the bronchoalveolar lavage fluid (BALF). The objective of this study was to characterize cytokine gene expression in the BALF cells of horses with IAD, including a comparison of cytokine gene expression between IAD horses with increased BALF mast cells (IAD-Mast) or neutrophils (IAD-Neutro). Methods: The mRNA expression of IL-4, IFN-γ, IL-17, IL-8, IL-1β, IL-5, IL-6, IL-10, IL-12p35, and eotaxin-2 was studied by quantitative polymerase chain ...
Alghamdi AS, Lovaas BJ, Bird SL, Lamb GC, Rendahl AK, Taube PC, Foster DN.Bovine semen is naturally deposited in the vagina and spermatozoa migrate through the cervix into the uterus leaving the bulk of seminal plasma (SP) behind. In equine, both spermatozoa and SP are deposited directly in the uterus and SP reduces sperm binding to neutrophils and prevents the formation of DNA-based neutrophil extracellular traps (NETs). We investigated the role of bovine SP on sperm-neutrophil binding using the four most common bovine semen extenders. Contrary to equine, bovine spermatozoa removed from SP had low binding to neutrophils for up to 3h, but as little as 10% SP increas...
Herteman N, Vargas A, Lavoie JP.Low-density neutrophils (LDNs) are a subset of neutrophils first described in the bloodstream upon pathological conditions, and recently, in the blood of healthy humans. LDNs may have an enhanced pro-inflammatory (low-density granulocytes, LDGs) or an immunosuppressive (Granulocytic myeloid-derived suppressor cells, G-MDSCs) profile. Whether these characteristics are specific to LDNs or related to disease states is unknown. Thus, we sought to investigate the properties of LDNs in both health and disease states, and to compare them to those of autologous normal-density neutrophils (NDNs). We st...
Debrue M, Hamilton E, Joubert P, Lajoie-Kadoch S, Lavoie JP.Recent finding suggests that T-cells may be involved in the pathogenesis of heaves in horses. However, little is known concerning their possible contribution to pulmonary neutrophilia, a characteristic finding in heaves. Interleukin (IL)-17 is a cytokine secreted by activated T-cells that indirectly promotes the maturation, chemotaxis and activation of neutrophils. We therefore hypothesized that IL-17 may be involved in the recruitment of neutrophils into the airways and that its mRNA expression would be increased in bronchoalveolar lavage (BAL) cells of horses with heaves. Heaves susceptible ...
Depecker M, Richard EA, Pitel PH, Fortier G, Leleu C, Couroucé-Malblanc A.The aim of this study was to determine whether the lung side being sampled would significantly influence bronchoalveolar lavage (BAL) cytological profiles and subsequent diagnosis in Standardbred racehorses. One hundred and thirty-eight French Trotters in active training and racing were included in a prospective observational study. BAL was performed using videoendoscopy in both right and left lungs during summer meetings in 2011 (64 horses) and 2012 (74 horses). Cytological data performed 24h later from right and left lungs were compared and specifically used to classify horses as affected wi...
Troedsson MH, Loset K, Alghamdi AM, Dahms B, Crabo BG.Insemination of mares with bacteria-free equine spermatozoa results in an influx of polymorphonuclear neutrophils (PMNs) into the uterine lumen. In vitro studies have demonstrated that equine spermatozoa activate complement, resulting in cleavage of factors C5a and C3b. Since uterine secretion is rich in complement, it is likely that an interaction between spermatozoa and uterine secretion results in C5a-mediated chemotaxis and migration of PMNs into the uterine lumen. Once in the uterine lumen, the PMNs phagocytize bacteria and spermatozoa, which is an important part of sperm elimination from...
Setlakwe EL, Lemos KR, Lavoie-Lamoureux A, Duguay JD, Lavoie JP.The consequences on lung function and inflammation of alterations in the extracellular matrix affecting the peripheral airway wall in asthma are largely unknown. We hypothesized that remodeling of collagen and elastic fibers in the peripheral airway wall leads to airway obstruction and contributes to neutrophilic airway inflammation. Animals used were six heaves-affected horses and five controls. Large peripheral lung biopsies were obtained from horses with heaves in clinical remission (Baseline) and during disease exacerbation and from age-matched controls. The area of collagen and elastic fi...
Hultén C, Demmers S.Differentiation between infectious and noninfectious disease and rapid initiation of accurate treatment are essential in managing diseases in the neonatal and young foal. Identification of useful inflammatory markers for these purposes is, therefore, of great importance. The aim of this study was to compare the responses of the acute phase protein serum amyloid A (SAA) with the responses of fibrinogen and total leucocyte and neutrophil counts in infectious diseases encountered in the young foal, and to assess whether SAA measurements give additional information useful in the management of thes...
Rebordão MR, Carneiro C, Alexandre-Pires G, Brito P, Pereira C, Nunes T, Galvão A, Leitão A, Vilela C, Ferreira-Dias G.Besides the classical functions, neutrophils (PMNs) are able to release DNA in response to infectious stimuli, forming neutrophil extracellular traps (NETs) and killing pathogens. The pathogenesis of endometritis in the mare is not completely understood. The aim was to evaluate the in vitro capacity of equine PMNs to secrete NETs by chemical activation, or stimulated with Streptococcus equi subspecies zooepidemicus (Szoo), Escherichia coli (Ecoli) or Staphylococcus capitis (Scap) strains obtained from mares with endometritis. Ex vivo endometrial mucus from mares with bacterial endometritis wer...
Zerbe H, Schuberth HJ, Engelke F, Frank J, Klug E, Leibold W.In order to investigate pathogenic mechanisms of acute endometritis in cows and mares, we established an in vivo model in both species. Based on the results of an in vitro transmigration system, human recombinant interleukin-8 (rhIL-8; 1.25 microg per mare and 5 microg per cow in 50 ml phosphate-buffered saline) was used to attract polymorphonuclear neutrophil granulocytes (PMNs) into the uteri. Peak numbers of uterine neutrophils were attracted after 6h, in both cows and mares. On average, mares responded more sensitively than cows, with 15 times higher numbers of rhIL-8-attracted uterine neu...
Jean D, Vrins A, Beauchamp G, Lavoie JP.To determine variations in cytologic counts of bronchoalveolar lavage (BAL) fluid attributable to month of collection, first and second aliquots, and left and right lung sites in horses with recurrent airway obstruction (RAO). Methods: 5 horses with RAO and 5 healthy horses without respiratory tract disease. Methods: Horses were housed in a stable for 5 months prior to and throughout the study. Bronchoalveolar lavage fluid was collected from the right and left lung of each horse 3 times at monthly intervals (February, March, and April). Each BAL fluid collection was performed by use of 2 incre...
Gerber V, Lindberg A, Berney C, Robinson NE.Mucus accumulation and neutrophilic inflammation in the airways are hallmarks of heaves. Endoscopically visible mucus accumulations, however, have not been studied during exposure to dusty hay and allergens (ie, environmental challenge). We hypothesized that (1) heaves-affected horses have increased mucus accumulation compared with controls, (2) mucus accumulations increase in heaves-affected horses during environmental challenge, and (3) environmental challenge also induces neutrophilic inflammation and mucus accumulation in control horses. Mucus accumulation was graded endoscopically (mucus ...
Côté O, Clark ME, Viel L, Labbé G, Seah SY, Khan MA, Douda DN, Palaniyar N, Bienzle D.Secretoglobin family 1A member 1 (SCGB 1A1) is a small protein mainly secreted by mucosal epithelial cells of the lungs and uterus. SCGB 1A1, also known as club (Clara) cell secretory protein, represents a major constituent of airway surface fluid. The protein has anti-inflammatory properties, and its concentration is reduced in equine recurrent airway obstruction (RAO) and human asthma. RAO is characterized by reversible airway obstruction, bronchoconstriction and neutrophilic inflammation. Direct effects of SCGB 1A1 on neutrophil functions are unknown. We have recently identified that the SC...
Hirsch G, Lavoie-Lamoureux A, Beauchamp G, Lavoie JP.Neutrophils are generally considered less responsive to glucocorticoids compared to other inflammatory cells. The reported increase in human neutrophil survival mediated by these drugs partly supports this assertion. However, it was recently shown that dexamethasone exerts potent anti-inflammatory effects in equine peripheral blood neutrophils. Few comparative studies of glucocorticoid effects in neutrophils and other leukocytes have been reported and a relative insensitivity of neutrophils to these drugs could not be ruled out. Objective: We assessed glucocorticoid-responsiveness in equine an...
Gerber V, Robinson NE, Luethi S, Marti E, Wampfler B, Straub R.Horses housed in conventional stable environments are exposed to high dust loads. Long-term exposure to inhaled dust may lead to subclinical airway disease. Objective: Airway inflammation and mucus accumulation are 1) common in asymptomatic well-performing sport horses, 2) increased in older compared to younger individuals and 3) correlated. Methods: Mucus quantity and quality (endoscopic scoring) and BALF differential cytology were assessed in 13 younger horses (mean age 5 years) and 13 older horses (mean age 15 years), which had no historical or clinical evidence of lower airway disease, wer...
