Macrophages are a type of white blood cell found in horses that play a significant role in the immune system. They are involved in the detection, phagocytosis, and destruction of bacteria and other harmful organisms. Additionally, macrophages contribute to tissue homeostasis and repair by removing dead cells and stimulating tissue regeneration. In horses, macrophages are distributed throughout various tissues, including the liver, lungs, and lymph nodes, where they help orchestrate the body's response to infection and injury. This page compiles peer-reviewed research studies and scholarly articles that explore the function, regulation, and clinical implications of macrophages in equine health.
Sun WC, Berghaus LJ, Moore JN, Hurley DJ, Vandenplas ML, Thompson R, Linden J.Stimulation of adenosine A(2A) receptors results in anti-inflammatory effects in a variety of cell types. Lipopolysaccharide (LPS) and pro-inflammatory cytokines, such as TNF-alpha and IL-1, have been reported to up-regulate the expression of adenosine A(2A) receptors and thereby enhance the functional activity of adenosine A(2A) receptors in human and murine monocyte/macrophage cell lines and in monocytes/macrophages isolated from those species. In this study, we investigated the effects of LPS and TNF-alpha on the expression and functional activity of adenosine A(2A) receptors in isolated eq...
Covaleda L, Fuller FJ, Payne SL.Equine infectious anemia virus (EIAV) infection is distinctive in that it causes a rapid onset of clinical disease relative to other retroviruses. In order to understand the interaction dynamics between EIAV and the host immune response, we explored the effects of EIAV and its S2 protein in the regulation of the cytokine and chemokine response in macrophages. EIAV infection markedly altered the expression pattern of a variety of pro-inflammatory cytokines and chemokines monitored in the study. Comparative studies in the cytokine response between EIAV(17) and EIAV(17DeltaS2) infection revealed ...
Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Fortes B, Thompson R, Linden J.Adenosine is an endogenous nucleoside that has potent receptor-mediated immunomodulatory effects on macrophage/monocyte function. In this study, we determined the effects of an adenosine A(2A) receptor agonist, ATL313, on the expression of mRNAs for four pro-inflammatory mediators, IL-1beta, IL-8, COX-2, and TNF-alpha, and the mRNA and protein for the anti-inflammatory cytokine, IL-10 in equine monocytes incubated with lipopolysaccharide (LPS). The results indicate that ATL313 significantly reduces LPS-induced expression of COX-2 and TNF-alpha, enhances the expression of IL-10 and IL-8, but do...
Doherty TJ.Surgical manipulation of the intestines activates intestinal macrophages that release cytokines and nitric oxide, which results in inhibition of intestinal motility. Subsequent infiltration of circulating leukocytes into the intestinal wall contributes to cytokine and nitric oxide release and exacerbates ileus. Other factors contributing to ileus are endotoxemia; edema of the intestine wall subsequent to excessive fluid therapy; hypocalcemia; and long abdominal incisions. Because treatment of ileus with prokinetic drugs has not proven to be very effective, efforts should be directed at reducin...
Schneberger D, Caldwell S, Suri SS, Singh B.Toll-like receptor 9 (TLR9) has been found to be the main receptor to respond to bacterial DNA in a wide variety of species. Recent work has shown that TLR9 is expressed in a diverse set of cells within the lung. However, much of this data has been centered on human and mouse cell culture lines or primary cultures and very little is known of TLR9 expression in intact lung, especially that of the horse. Here we show that TLR9 is expressed in the lungs of horses in a wide variety of cells. In particular, we note expression in pulmonary intravascular macrophages (PIMs), alveolar macrophages, bron...
von Bargen K, Haas A.The soil actinomycete Rhodococcus equi is a pulmonary pathogen of young horses and AIDS patients. As a facultative intracellular bacterium, R. equi survives and multiplies in macrophages and establishes its specific niche inside the host cell. Recent research into chromosomal virulence factors and into the role of virulence plasmids in infection and host tropism has presented novel aspects of R. equi infection biology and pathogenicity. This review will focus on new findings in R. equi biology, the trafficking of R. equi-containing vacuoles inside host cells, factors involved in virulence and ...
Pargass IS, Wills TB, Davis WC, Wardrop KJ, Alperin DC, Hines SA.There is a distinct age-associated susceptibility of horses to Rhodococcus equi infection. Initial infection is thought to occur in the neonatal and perinatal period, and only foals less than 6 months of age are typically affected. R. equi is closely related and structurally similar to Mycobacterium tuberculosis, and causes similar pathologic lesions. Protective immune responses to M. tuberculosis involve classical major histocompatibility complex (MHC)-restricted T cells that recognize peptide antigen, as well as MHC-independent T cells that recognize mycobacterial lipid antigen presented by ...
Fidalgo-Carvalho I, Craigo JK, Barnes S, Costa-Ramos C, Montelaro RC.EIAV is a monocyte/macrophage tropic virus. To date, even though EIAV has been under investigation for numerous years, very few details have been elucidated about EIAV/macrophage interactions. This is largely due to the absence of an equine macrophage cell line that would support viral replication. Herein we describe the spontaneous immortalization and generation of a clonal equine macrophage-like (EML) cell line with the functional and immunophenotype characteristics of differentiated equine monocyte derived macrophage(s) (eMDM(s)). These cells possess strong non-specific esterase (NSE) activ...
Ferraz LC, Bernardes ES, Oliveira AF, Ruas LP, Fermino ML, Soares SG, Loyola AM, Oliver C, Jamur MC, Hsu DK, Liu FT, Chammas R, Roque-Barreira MC.Galectin-3 is a beta-galactoside-binding lectin implicated in the fine-tuning of innate immunity. Rhodococcus equi, a facultative intracellular bacterium of macrophages, causes severe granulomatous bronchopneumonia in young horses and immunocompromised humans. The aim of this study is to investigate the role of galectin-3 in the innate resistance mechanism against R. equi infection. The bacterial challenge of galectin-3-deficient mice (gal3-/-) and their wild-type counterpart (gal3+/+) revealed that the LD50 for the gal3(-/-) mice was about seven times higher than that for the gal3+/+ mice. Wh...
Morrison LR, Freel K, Henderson I, Hahn C, Smith SH.Lymphoma (malignant lymphoma, lymphosarcoma) is uncommon in horses in the United Kingdom. This report describes an unusual form of lymphoproliferative disease with features of lymphoma restricted to the central nervous system (CNS) and with no evidence of a primary lesion elsewhere. Immunohistochemical examination defined an overwhelming predominance of T lymphocytes with admixed B lymphocytes and activated macrophages. This case exemplifies the challenges associated with definitive diagnosis of lymphoproliferative disease of the equine CNS.
Sponseller BA, de Macedo MM, Clark SK, Gallup JM, Jones DE.Foals are particularly vulnerable to infection by Rhodococcus equi during the first 2 weeks of life whereas mature horses are not. While an innate immunodeficiency likely accounts for this clinically relevant vulnerability, the factors that contribute to infection by R. equi have not been fully elucidated. In this study, we demonstrate that cells of the monocyte lineage, including monocytes, macrophages, and dendritic cells, that have been activated with LPS and IFN-gamma, respond with a statistically significant, greater amount of cytokine mRNA production of IL-10, IL-12p35, and IL-12p40 than...
Stokol T, Gold J, Johnson A, Ainsworth D.A 3-day-old filly was presented to the Cornell University Hospital for Animals with an umbilical hematoma and mild aspiration pneumonia. The foal underwent abdominal surgery for resection of the hematoma. Recovery was uneventful, but 3 days after surgery, the foal became progressively tachypneic. Imaging studies revealed bilateral pleural effusion and pleuropneumonia. Cytologic evaluation and bacterial culture of the pleural fluid from both sides of the chest revealed sterile exudates, consisting mostly of neutrophils, with fewer macrophages and lymphocytes. Pleural fluid macrophages contained...
Pratt SM, Christian JA, Paige Jackson L, Hawkins JF, Sojka JE.A 16-year-old castrated male Arabian horse was presented to the Purdue University Veterinary Teaching Hospital with a 4-hour history of colic. Initial examinations provided strong evidence for small intestinal obstruction. Abdominal surgery revealed a strangulating lipoma, and 25 feet of small intestine were resected. Postoperatively, the horse developed obstructive ileus due to adhesion formation, which required a second laparotomy. During and after surgery, the abdomen was lavaged with sodium carboxymethylcellulose (CMC). One week after the second surgery, evaluation of peritoneal fluid reve...
Mäkinen PE, Archer DC, Baptiste KE, Malbon A, Proudman CJ, Kipar A.Idiopathic focal eosinophilic enteritis (IFEE) and diffuse eosinophilic enteritis (DEE) are primary eosinophilic intestinal conditions without a known cause that are associated with an increasing number of surgical colic cases. Histology may be helpful in defining disease aetiology and pathogenesis. Objective: To characterise further the inflammatory infiltrate in equine IFEE and to compare the condition with DEE. Methods: Twenty-three IFEE cases and 5 DEE cases were examined by light microscopy including immunohistology to identify infiltrating leucocytes. Inflammatory infiltrates in mucosa a...
Lemos KR, Marques LC, Deaquino LP, Alessi AC, Machado RZ.An histochemical and immunohistochemical study was carried out to evaluate the mechanisms of immune response of horses experimentally infected by Trypanosoma evansi. For this purpose the HE histochemical stain and the avidin biotin peroxidase method were used. To determine the presence and immunoreactivity of immune cells we used anti-major histocompatibility complex II antibodies. Cellular infiltration phenotype was characterized with the aid of anti-CD3 antibody for T lymphocytes and by anti-BLA 36 antibodies for B lymphocytes. Macrophages were marked with an antibody against myeloid/histyoc...
Sydor T, von Bargen K, Becken U, Spuerck S, Nicholson VM, Prescott JF, Haas A.Rhodococcus equi is a mucoid Gram-positive facultative intracellular pathogen which can cause severe bronchopneumonia in foals and AIDS patients. A polysaccharide capsule which gives R. equi a mucoid appearance has long been suspected to be a virulence factor. Here, we describe a transposome mutant in the gene fbpA of strain R. equi 103 causing absence of a capsular structure. FbpA is a chromosomal gene homologous to antigen 85 (Ag85) mycolyl chain transferase gene of Mycobacterium tuberculosis. The mutant multiplied normally in isolated macrophages, was able to establish the unusual R. equi-c...
Martens RJ, Mealey K, Cohen ND, Harrington JR, Chaffin MK, Taylor RJ, Bernstein LR.To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in healthy foals. Methods: 6 healthy neonatal foals. Methods: Each foal received GaM (20 mg/kg) by intragastric administration. Blood samples were obtained before (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours after GaM administration for determination of serum gallium concentrations by use of inductively coupled plasma mass spectroscopy. Results: Mean +/- SD pharmacokinetic variables were as follows: peak serum gallium concentration, 1,079 +/- 311 ng/mL; time to peak serum concentra...
Xu Y, Jia Z, Zhou L, Wang L, Li J, Liang Y, Zhao T, Ni B, Wu Y.To warrant potential clinical testing, the equine anti-SARS-CoV F(ab')(2) requires evaluation in as many animal models as possible and a safety test in a primate model. In this study, we evaluated the pharmacokinetics, tolerance and immunity of this kind of antibody in macaques and rats. Results showed that the F(ab')(2) fragments had a normal metabolism in injected animals. The general physiological indexes did not differ between animals injected with anti-SARS-CoV F(ab')(2) or saline. However, a mild inflammatory response in local injection site and a moderate immune response against this an...
Allen CA, Payne SL, Harville M, Cohen N, Russell KE.The study of the equine immune system and inflammatory responses, by measuring cytokine expression, can provide important insight into disease pathogenesis in the horse. A set of quantitative real-time polymerase chain reaction (QPCR) assays for the equine cytokines IL-1alpha, IL-1beta, IL-6, IL-8 and TNF-alpha were validated using QPCR primers and probes which were generated for the equine IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha and 18S genes. Amplification efficiency, intra-assay and inter-assay variation were determined using 10-fold dilutions of plasmid for each gene. Under these condit...
Lewis SS, Valberg SJ, Nielsen IL.Although immune-mediated myositis (IMM) is commonly reported in other species, this condition is poorly described in horses. Objective: IMM occurs in horses. Methods: Thirty-seven horses with suspected IMM were included in the study. Methods: The database of the Neuromuscular Diagnostic Laboratory was reviewed to identify 37 horses with muscle biopsies characterized by lymphocytic infiltrates. A retrospective standardized questionnaire regarding clinical signs and response to treatment was answered by horse owners. Results: Horses with suspected IMM were predominantly of Quarter Horse bloodlin...
Pearson W, Charch A, Brewer D, Clarke AF.Recurrent airway obstruction (RAO), known previously as chronic obstructive pulmonary disease (COPD), is a debilitating respiratory condition that significantly contributes to lost training days and illness in racehorses. Herbs are becoming increasingly popular for the prophylaxis or treatment of the clinical signs of RAO despite a paucity of research on efficacy and safety. We evaluated the ability of an herbal composite containing garlic, white horehound, boneset, aniseed, fennel, licorice, thyme, and hyssop to reduce the clinical signs of RAO, hypothesizing that the product would safely red...
Bryant CE, Ouellette A, Lohmann K, Vandenplas M, Moore JN, Maskell DJ, Farnfield BA.Sepsis and endotoxaemia are important causes of morbidity and mortality in humans. Research on sepsis focuses on rodent models most of which are poorly responsive to lipopolysaccharide (LPS), and thus do not mimic very well the high sensitivity of humans. Therefore, there is a need to develop more clinically relevant models. Horses suffer from a similar endotoxaemic syndrome to humans with high morbidity and mortality. LPS analogues that act as antagonists at Toll-like receptor 4 (TLR4) are being developed as novel treatments for endotoxaemia. Due to differences in recognition of ligands by TL...
Pei Y, Parreira V, Nicholson VM, Prescott JF.Rhodococcus equi can cause severe or fatal pneumonia in foals as well as in immunocompromised animals and humans. Its ability to persist in macrophages is fundamental to how it causes disease, but the basis of this is poorly understood. To examine further the general application of a recently developed system of targeted gene mutation and to assess the importance of different genes in resistance to innate immune defenses, we disrupted the genes encoding high-temperature requirement A (htrA), nitrate reductase (narG), peptidase D (pepD), phosphoribosylaminoimidazole-succinocarboxamide synthase ...
Tu YB, Zhou T, Yuan XF, Qiu HJ, Xue F, Sun CQ, Wang L, Wu DL, Peng JM, Kong XG, Tong GZ.The long terminal repeats (LTRs) of equine infectious anemia virus donkey leukocyte-attenuated virus (EIAV-DLA) were substituted with those of the wild-type EIAV-L (wt EIAV-L, the parent virus of EIAV-DLA). The resulting chimeric plasmid was designated pOK-LTR DLA/L. Purified pOK-LTR DLA/L was transfected into monocyte-derived macrophage (MDM) cultures prepared from EIAV-negative, heparinized whole blood from a donkey. Eighth-passage cell cultures developed the typical cytopathogenic effects (CPE) of EIAV infection, and virions with typical EIAV profiles were observed with an electron microsco...
Pei Y, Dupont C, Sydor T, Haas A, Prescott JF.To analyze further the role in virulence of the prominent cholesterol oxidase (ChoE) of Rhodococcus equi, an allelic exchange choE mutant from strain 103+ was constructed and assessed for virulence in macrophages, in mice, and in foals. There was no difference between the mutant and parent strain in cytotoxic activity for macrophages or in intra-macrophage multiplication. No evidence of attenuation was obtained in macrophages and in mice, but there was slight attenuation apparent in four intra-bronchially infected foals compared to infection of four foals with the virulent parent strain, based...
Sledge DG, Miller DL, Styer EL, Hydrick HA, Baldwin CA.Granulomatous dermatitis in horses has been linked to many etiologies, including various parasites, fungi, and bacteria. Idiopathic forms of granulomatous inflammation-producing diseases, some of which are localized to the skin, also have been reported in horses. Herein we describe a case of recurrent equine granulomatous skin disease characterized by intranuclear viral inclusions within macrophages and giant cells. The histologic changes were primarily noted in the deep dermis and included multifocal to coalescing areas of necrosis marked by histiocytic cell infiltration and presence of giant...
Laan TT, Bull S, van Nieuwstadt RA, Fink-Gremmels J.Beta-agonists have been shown to display anti-inflammatory properties in several experimental models. The aim of this study was to investigate the anti-inflammatory properties of clenbuterol (CB), administered either intravenously or by aerosol, in comparison with fluticasone propionate (FP) in recurrent airway obstruction (RAO)-susceptible horses. Eight horses, of which five were known to be susceptible to RAO, underwent an inhalation challenge with Aspergillus fumigatus (AF) antigen and were treated with CB intravenously, CB by aerosol, or FP by aerosol. Twenty-four hours after the challenge...
Wyse CA, Nixon C, McLaughlin M, Dowell FJ, Philbey AW.The aim of this study was to characterise the expression of haem oxygenase-1 (HO-1) in healthy lung tissue from horses and to measure its activity. Samples of lung tissue were collected from six horses euthanased for reasons other than respiratory disease. HO-1 expression and activity were detected in type II alveolar epithelial cells, macrophages and neutrophils in all the samples examined. The activity was dependent on the presence of NADPH and inhibited quantitatively by the addition of increasing concentrations of a competitive inhibitor of HO-1, tin mesoporphyrin IX.
Singh Suri S, Janardhan KS, Parbhakar O, Caldwell S, Appleyard G, Singh B.Toll-like receptor (TLR) is a key component in launching innate immune response to microbial challenge. TLR4 and TLR2 are recognized as specific receptors for components of Gram-negative and Gram-positive bacteria, respectively. Horses are extremely sensitive to endotoxin-induced cardiopulmonary distress and mortality which causes significant economic losses. To date, there are no data on the expression of TLR4 and TLR2 in horse lungs. Therefore, we examined the expression of TLR4 and TLR2 in lungs from normal or Escherichia coli lipopolysaccharide (E. coli LPS; 50 ng/kg; iv) treated horses. W...
Morresey PR, Mackay RJ.To measure serum polymyxin B concentration after single and repeated IV infusions in horses. Methods: 5 healthy horses. Methods: In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion a...
Sun WC, Berghaus LJ, Moore JN, Hurley DJ, Vandenplas ML, Thompson R, Linden J.Stimulation of adenosine A(2A) receptors results in anti-inflammatory effects in a variety of cell types. Lipopolysaccharide (LPS) and pro-inflammatory cytokines, such as TNF-alpha and IL-1, have been reported to up-regulate the expression of adenosine A(2A) receptors and thereby enhance the functional activity of adenosine A(2A) receptors in human and murine monocyte/macrophage cell lines and in monocytes/macrophages isolated from those species. In this study, we investigated the effects of LPS and TNF-alpha on the expression and functional activity of adenosine A(2A) receptors in isolated eq...
Koivunen AL, Maisi P, Konttinen YT, Prikk K, Sandholm M.The collagenolytic activity and its sensitivity to doxycycline inhibition in tracheal aspirates (TA) of horses with chronic obstructive pulmonary disease (COPD) was analyzed with SDS-PA gel electrophoresis (SDS-PAGE), using Type 1 collagen as the substrate. Both autoactive and total collagenase activities were significantly higher in TAs of horses with symptomatic COPD than in TAs of healthy horses. Doxycycline inhibition studies suggest that most of the TA collagenase is of the neutrophil type (MMP-8), but some is derived from other cells such as fibroblasts and monocyte/macrophages (MMP-1) a...
Hines R, Sorensen BR, Shea MA, Maury W.Binding of the transcription factor PU.1 to its DNA binding motif regulates the expression of a number of B-cell- and myeloid-specific genes. The long terminal repeat (LTR) of macrophage-tropic strains of equine infectious anemia virus (EIAV) contains three PU.1 binding sites, namely an invariant promoter-proximal site as well as two upstream sites. We have previously shown that these sites are important for EIAV LTR activity in primary macrophages (W. Maury, J. Virol. 68:6270-6279, 1994). Since the sequences present in these three binding motifs are not identical, we sought to determine the r...
Muehlmann LA, Michelotto PV, Nunes EA, Grando FC, da Silva FT, Nishiyama A.Phagocytosis exerted by alveolar macrophages and neutrophils is crucial in the clearance of exogenous particles deposited in the airways. Therefore, substances that activate these phagocytes in the airways can exert important effects on the particle clearance rate. PAF, particularly, was proved to be a potent activator of several immune cells and was shown to be present in the equine lower airways in specific conditions, such as after exercise. The present study aimed to investigate if PAF is able to increase the phagocytic capacity and the production of superoxide anion in equine alveolar mac...
Zink MC, Yager JA, Prescott JF, Wilkie BN.Bronchoalveolar lavage was performed 5 times, sequentially, on 3 healthy foals while each foal was 6 to 63 days of age. Phagocytosis and bactericidal assays were performed on recovered alveolar macrophages. Corynebacterium equi and alveolar macrophages at a ratio of 10:1 were incubated for 1 hour in medium containing 1% heat-inactivated rabbit anti-C equi serum. After incubation, greater than 90% of the alveolar macrophages contained at least 1 ingested bacterium and each alveolar macrophage contained 9.4 +/- 1.0 bacteria (mean +/- SE). After alveolar macrophages and C equi were incubated for ...
Xu Y, Jia Z, Zhou L, Wang L, Li J, Liang Y, Zhao T, Ni B, Wu Y.To warrant potential clinical testing, the equine anti-SARS-CoV F(ab')(2) requires evaluation in as many animal models as possible and a safety test in a primate model. In this study, we evaluated the pharmacokinetics, tolerance and immunity of this kind of antibody in macaques and rats. Results showed that the F(ab')(2) fragments had a normal metabolism in injected animals. The general physiological indexes did not differ between animals injected with anti-SARS-CoV F(ab')(2) or saline. However, a mild inflammatory response in local injection site and a moderate immune response against this an...
Current HIV researchMarch 10, 2010
Volume 8, Issue 1 66-72 doi: 10.2174/157016210790416352
Payne SL, Fuller FJ.Equine infectious anemia virus (EIAV) is a macrophage-tropic lentivirus that rapidly Induces disease in experimentally infected horses. Because EIAV infection and replication is centered on the monocyte/macrophage and has a pronounced acute disease stage, it is a useful model system for understanding the contribution of monocyte/macrophages to other lentivirus-induced diseases. Genetic mapping studies utilizing chimeric proviruses in which parental viruses are acutely virulent or avirulent have allowed the identification of important regions that influence acute virulence. U3 regions in the vi...
Morris DD, Crowe N, Moore JN, Moldawer LL.A study was performed to determine whether equine peritoneal macrophages produce interleukin 6 (IL-6) in vitro in response to endotoxin. Peritoneal fluid was collected from 14 clinically normal adult horses and was used as the source of peritoneal macrophages. Macrophages from each horse were isolated and cultured separately in vitro in the absence or presence of various concentrations (0.5, 5, 500 ng/ml) of endotoxin (lipopolysaccharide from Escherichia coli 055:B5). Culture medium supernatants were collected after 3, 6, 12, and 24 hours' incubation and were frozen at -70 C until assayed for ...
Zamith Cunha R, Semprini A, Salamanca G, Gobbo F, Morini M, Pickles KJ, Roberts V, Chiocchetti R.Cannabinoid receptors are expressed in human and animal trigeminal sensory neurons; however, the expression in the equine trigeminal ganglion is unknown. Ten trigeminal ganglia from five horses were collected post-mortem from an abattoir. The expression of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), and the cannabinoid-related receptors like transient receptor potential vanilloid type 1 (TRPV1), peroxisome proliferator-activated receptor gamma (PPARɣ), and G protein-related receptor 55 (GPR55) in the trigeminal ganglia (TG) of the horse were studied, using immunofluorescence on cry...
Sage SE, Leeb T, Jagannathan V, Gerber V.Severe equine asthma (SEA) is a complex respiratory condition characterized by chronic airway inflammation. It shares many clinical and pathological features with human neutrophilic asthma, making it a valuable model for studying this condition. However, the immune mechanisms driving SEA have remained elusive. Although SEA has been primarily associated with a Th2 response, there have also been reports of Th1, Th17, or mixed-mediated responses. To uncover the elusive immune mechanisms driving SEA, we performed single-cell mRNA sequencing (scRNA-seq) on cryopreserved bronchoalveolar cells from 1...
Bueno BL, Câmara RJF, Moreira MVL, Galinari GCF, Souto FM, Victor RM, Bicalho JM, Ecco R, Dos Reis JKP.Equine infectious anemia (EIA), a disease caused by equine infectious anemia virus (EIAV), is considered an obstacle to the development of the horse industry. There is no treatment or vaccine available for EIA, and its pathogenesis, as well as the immune response against the virus, is not fully understood. Therefore, an immunohistochemistry assay was developed for the detection of viral antigens in tissues of equids naturally infected with EIAV. Sections of organs of six equids from Apodi-RN, Brazil, that tested positive for EIA by serological tests (ELISA and AGID) were fixed in 10% formalin ...
Zink MC, Johnson JA.Bronchoalveolar lavage was performed 5 times, sequentially, on 3 healthy foals when each was between 2 and 63 days of age. Total and differential counts were performed on recovered cells. The lungs of foals less than 19 days of age contained few alveolar macrophages recoverable by bronchoalveolar lavage. This number increased sharply during the first 2 to 3 weeks of life, but remained relatively constant subsequently. Approximately 86% of the alveolar cells in the lungs of foals up to 3 weeks of age were alveolar macrophages. During the first 2 months of life, this number decreased to approxim...
Schumacher HR.The normal synovial membrane as seen by electron microscopy is bordered by one to three layers of lining cells that include some with phagocytic function, others rich in endoplasmic reticulum for protein synthesis and additional cells with mixed properties. Lining cells with prominent Golgi apparatus probably produce the synovial hyaluronic acid. The synovial matrix contains collagen and mucopolysaccharide. It offers little barrier to diffusion of most materials. Superficial capillaries and venules are fenestrated and presumably allow rapid exchange of fluid and electrolytes. Deeper venules ha...
Raidal SL, Love DN, Bailey GD, Rose RJ.The effect of strenuous exercise on the functional capacity of pulmonary alveolar macrophages (PAM) and bronchoalveolar lavage-derived lymphocytes was determined in eight horses prior to and after 7 weeks of training. Strenuous exercise had no effect on the total cell count or the percentage of live cells in bronchoalveolar lavage (BAL) samples prior to or following training. However, training was associated with a significant increase in the total cell count of pre-exercise BAL samples and a significant reduction in the percentage of live cells in post-exercise samples. Strenuous exercise was...
Waldschmidt I, Pirottin D, Art T, Audigié F, Bureau F, Tosi I, El Abbas S, Farnir F, Richard E, Dupuis MC.Pulmonary diseases are common in horses and have a major economic impact on the equine industry. Some of them could be associated with an inadequate immune response in the lung, but methods to evaluate this response in horses are lacking. The aim of this study was to develop and validate an experimental model that could be applied in several physiological and pathological conditions to assess the innate immune response of equine pulmonary cells. Equine alveolar macrophages (AMs) obtained from bronchoalveolar lavages were isolated from other cells by adhesion. TLR2, 3, and 4 expression in AMs w...
Fidalgo-Carvalho I, Craigo JK, Barnes S, Costa-Ramos C, Montelaro RC.EIAV is a monocyte/macrophage tropic virus. To date, even though EIAV has been under investigation for numerous years, very few details have been elucidated about EIAV/macrophage interactions. This is largely due to the absence of an equine macrophage cell line that would support viral replication. Herein we describe the spontaneous immortalization and generation of a clonal equine macrophage-like (EML) cell line with the functional and immunophenotype characteristics of differentiated equine monocyte derived macrophage(s) (eMDM(s)). These cells possess strong non-specific esterase (NSE) activ...
Smith TA, Davis E, Carpenter S.Lentiviruses replicate in cells of the immune system, and activation of immune cells has been shown to modulate virus replication. To determine the effects of macrophage activation on replication of equine infectious anaemia virus (EIAV), primary horse macrophage cultures (HMCs) were established from 20 different horses, infected with an avirulent strain of EIAV, and stimulated with 5 microg/ml of bacterial endotoxin. Supernatants collected from HMCs were assayed for the presence of tumour necrosis factor (TNF-alpha) and for production of infectious virus. Results indicated that EIAV replicati...
Morris DD, Moore JN, Fischer K, Tarleton RL.A study was performed to determine whether equine macrophages produce tumor necrosis factor (TNF) activity in vitro in response to endotoxin and to study the effects of endotoxin concentration and incubation time on the amount of TNF produced. Equine peritoneal macrophages were isolated and cultured in vitro for 2, 6, 12, or 24 hr in tissue culture media containing 1) no additive (nonstimulated control), 2) endotoxin (0.5 ng/ml, 5 ng/ml, or 5 micrograms/ml), or 3) the calcium ionophore A23187 (0.95 microM). The supernatant media concentrations of TNF activity were determined by an in vitro cyt...
Michelotto PV, Muehlmann LA, Zanatta AL, Bieberbach EW, Fernandes LC, Nishiyama A.Inflammatory airway disease (IAD) is prevalent in young racehorses during training, being the 2nd most commonly diagnosed ailment interrupting training of 2-year-old Thoroughbred racehorses. Objective: That stabling and exercise cause oxidative stress, release of platelet-activating factor (PAF) and inflammation in airways of Thoroughbred colts. Methods: Colts in breeding farms (NC, n = 45), stabled for 30 days (EC, n = 40), and race trained (EX, n = 34). Methods: Cytological profile and parameters of bronchoalveolar lavage fluid (BALF) related to oxidative stress, bioactivity of the proinflam...
Carrasco L, Sánchez C, Gómez-Villamandos JC, Laviada MD, Bautista MJ, Martínez-Torrecuadrada J, Sánchez-Vizcaíno JM, Sierra MA.African horse sickness (AHS) is a disease of equids, characterized by severe pulmonary oedema and caused by an orbivirus. To determine the role of pulmonary intravascular macrophages (PIMs) in the development of pulmonary microvascular changes in this disease, five horses were given an intravenous inoculation of 10(6)TCID50of serotype 4 of AHS virus. Viral replication was detected in endothelial cells, PIMs, interstitial macrophages and fibroblasts. Alveolar and interstitial oedema, and changes in pulmonary microvasculature, consisting mainly of the sequestration of neutrophils and the formati...
Dutta SK, Campbell DL.Equine macrophages from the mammary glands of a yearling filly and an 18-year-old barren nonlactatind mare formed cell monolayers in continuous cultures. There was absence of viral cytopathic effect (CPE) in early cell culture passages. The cells from the early cell culture passages having no CPE failed to show evidence of virus or viral antigen by electron microscopic and immunofluorescence studies. Foci of CPE first appeared in the monolayer cell cultures from the filly and the mare in the 3rd and the 4th serial passages respectively, and the CPE increased on subsequent serial passages. Equi...
Mair TS, Stokes CR, Bourne FJ.Lavage procedures were used to obtain samples of respiratory secretions from the nasal cavity, trachea, bronchi and bronchoalveolar level of apparently normal conscious horses, and the cellular composition of the lavage fluids was assessed. There was a progressive increase in total cell count of the secretions obtained from the upper to the lower respiratory tracts. Nasal lavage fluid was composed chiefly of epithelial cells, whereas tracheal, bronchial and bronchoalveolar fluids contained higher proportions of macrophages, lymphocytes and neutrophils. Eosinophils and mast cells were identifie...
Witonsky S, Buechner-Maxwell V, Santonastasto A, Pleasant R, Werre S, Wagner B, Ellison S, Lindsay D.Equine protozoal myeloencephalitis (EPM) is a common and devastating neurologic disease of horses in the United States. Because some EPM-affected horses have decreased immune responses, immunomodulators such as levamisole have been proposed as supplemental treatments. However, little is known about levamisole's effects or its mechanism of action in horses. Objective: Levamisole in combination with another mitogen will stimulate a macrophage 1 (M1), dendritic cell 1 (DC1), T-helper 1 (CD4 Th1), and T-cytotoxic (CD8) immune response in equine peripheral blood mononuclear cells (PBMCs) in vitro a...
Sentsui H, Kono Y.Horse erythrocytes treated with equine infectious anemia virus hemagglutinin were phagocytized by cultivated horse leukocytes (mainly macrophage-like cells and partly polymorphonuclear cells) after incubation with fresh horse serum but not with inactivated horse serum. The phagocytosis began as soon as the erythrocytes were added to the leukocyte cultures, and the majority of the reaction proceeded within 30 minutes. Addition of antiserum showed a slightly suppressing but no enhancing effect on the phagocytosis. Phagocytosis seemed to be caused by the recognition of the third complement compon...
Hondalus MK, Sweeney CR, Mosser DM.A Rhodococcus equi radiobinding assay has been developed using organisms labeled with 3H-uracil. These labeled organisms resemble their unlabeled counterparts with respect to colony morphology, viability, and buoyant density. Bacteria routinely incorporate between 5 x 10(-3) and 5 x 10(-2) counts per minute per colony forming unit (cfu) which in this assay allows the detection of fewer than 0.2 cfu per macrophage. Once incorporated, greater than 90% of the label remains bacterial associated for at least 4 h postlabeling. The majority of the label is trichloroacetic acid precipitable, partition...
Hills BA, Ethell MT, Hodgson DR.This study was undertaken to determine whether glucocorticosteroids promote the secretion of lubricating surfactant, i.e. surface-active phospholipid (SAPL), into the joint. A standard clinical dose (100 mg) of methylprednisolone acetate (MPA) in 2.5 ml of saline was injected into the load-bearing right radiocarpal joint of five horses and 2.5 ml of saline injected into each of the contralateral joints used as controls. Synovial fluid (SF) was aspirated from all 10 joints before injection and at intervals of 16 and 32 h after injection, and then analysed by standard methods. All test joints sh...
Platt H.A series of 10 haemorrhagic polyps of the equine nasal cavity is described. The lesions show haematoma formation, abundant haemosiderin in macrophages and giant cells, and organising fibrous tissue. In one case, angiomatoid lesions were observed in the mucous membrane of the paranasal sinuses and it is suggested that some haemorrhagic nasal polyps may originate from pre-existing haemangiomatous areas in the respiratory mucosa.
Ryan C, Giguère S, Fultz L, Long MT, Crawford PC.The objective of this study was to determine the effect of immunostimulants on neutrophil, macrophage, and lymphocyte function following ex vivo exposure to Rhodococcus equi. Eighteen foals were randomly assigned to one of 3 treatment groups. Treatment consisted of inactivated Propionibacterium acnes (PA), inactivated parapoxvirus ovis (PPVO), or saline (control) administered on days 0 (7 days of age), 2, and 8. Bronchoalveolar lavage (BAL) fluid and blood were collected on days 0 (baseline), 12, 24 and 36. Intracellular replication of R. equi in macrophages, cytokine induction by R. equi-infe...
Rush BR, Flaminio MJ.Nonspecific immunomodulators are substances that induce non-antigen-specific enhancement of the body's native or acquired defense mechanisms. Immunomodulant preparations are most often used for treatment of chronic, viral, or bacterial infection with evidence of secondary immunosuppression. The proposed mechanism of action of these products is macrophage activation and subsequent release of cytokines that enhance humoral and cell-mediated immunity. In equine medicine, nonspecific immunostimulant products are used for prevention and treatment of infectious respiratory disease and treatment of s...
Bayerova Z, Janova E, Matiasovic J, Orlando L, Horin P.Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in ...
