American journal of physiology. Lung cellular and molecular physiology.
Publisher:
American Physiological Society,
Frequency: Twice monthly, 2012-
Country: United States
Language: English
Author(s):
American Physiological Society (1887- )
Start Year:1989 -
ISSN:
1040-0605 (Print)
1522-1504 (Electronic)
1040-0605 (Linking)
1522-1504 (Electronic)
1040-0605 (Linking)
Impact Factor
4.9
2022
| NLM ID: | 100901229 |
| (OCoLC): | 18304294 |
| Coden: | APLPE7 |
| LCCN: | 89646845 |
| Classification: | W1 AM507L |
Depletion of pulmonary intravascular macrophages rescues inflammation-induced delayed neutrophil apoptosis in horses. The objective of this study was to determine the effect of pulmonary intravascular macrophage depletion on systemic inflammation and ex vivo neutrophil apoptosis using an experimental model of intestinal ischemia and reperfusion injury in horses. Neutrophils were isolated before and after surgery from horses that were randomized to three treatment groups, namely, sham celiotomy (CEL, = 4), intestinal ischemia and reperfusion (IR, = 6), and intestinal ischemia and reperfusion with gadolinium chloride treatment to deplete pulmonary intravascular macrophages (PIMs, IRGC, = 6). Neutrophil apopt...
MicroRNA-221 is overexpressed in the equine asthmatic airway smooth muscle and modulates smooth muscle cell proliferation. Airway wall remodeling, including hyperplasia and hypertrophy of smooth muscle (ASM) cells leading to an increased smooth muscle mass, is considered central to asthma. However, molecular pathways responsible for ASM remodeling remain poorly understood. MicroRNAs (miRNAs) have emerged as key regulators of inflammatory and repair processes affecting the lungs and can downregulate protein expression by inhibiting target mRNA translation. We therefore hypothesized that miRNAs are involved in ASM remodeling in asthma by modulating ASM proliferation. We have analyzed the expression of miRNAs in bron...
Maintenance of contractile function of isolated airway smooth muscle after cryopreservation. Isolated human airway smooth muscle (ASM) tissue contractility studies are essential for understanding the role of ASM in respiratory disease, but limited availability and cost render storage options necessary for optimal use. However, to our knowledge, no comprehensive study of cryopreservation protocols for isolated ASM has been performed to date. We tested several cryostorage protocols on equine trachealis ASM using different cryostorage media [1.8 M dimethyl sulfoxide and fetal bovine serum (FBS) or Krebs-Henseleit (KH)] and different degrees of dissection (with or without epithelium and c...
Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses. Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, ...
Airway collagen and elastic fiber content correlates with lung function in equine heaves. 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...
Pulmonary intravascular macrophages as proinflammatory cells in heaves, an asthma-like equine disease. Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered by dust components such as endotoxin and has similarities to human asthma. Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to endotoxin-induced lung inflammation; however, their role in an airborne pathology remains unknown. Therefore, we investigated the role of PIMs in the development of heaves in horses. Clinical and inflammatory responses were evaluated following induction of heaves by moldy hay exposure and PIM depletion with gadolinium chloride (GC). Mares (N = 9) were exposed to four ...
IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo. Neutrophils are potent contributors to the lung pathophysiological changes occurring in allergic airway inflammation, which typically involve T helper type 2 (Th2) cytokine overexpression. We have previously reported that equine pulmonary endothelial cells are activated by the Th2 cytokine IL-4 and express chemotactic factors for neutrophils after stimulation. We have further explored the possible mechanisms linking Th2-driven inflammation and neutrophilia by studying the effects of recombinant equine IL-4, a prototypical Th2 cytokine, on peripheral blood neutrophils (PBN) isolated from normal...
IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells. Little is known concerning the possible contribution of T helper 2 (Th2)-type cytokines to the recruitment of neutrophils into the lung tissue. In the present study, endothelial cells from equine pulmonary arteries were cultured in the presence of recombinant equine (re) IL-4 and reIL-5, and the cytokine mRNA expression of molecules implicated in the chemotaxis and migration of neutrophils was studied using real-time RT-PCR. The functional response of reIL-4-induced endothelial cell stimulation on neutrophil migration was also studied using a chemotaxis chamber. ReIL-4 either increased the exp...
Muc5b and Muc5ac are the major oligomeric mucins in equine airway mucus. Horses frequently suffer from respiratory diseases, which, irrespective of etiology, are often associated with airway mucus accumulation. Studies on human airways have shown that the key structural components of the mucus layer are oligomeric mucins, which can undergo changes of expression and properties in disease. However, there is little information on these gel-forming glycoproteins in horse airways mucus. Therefore, the aims of this study were to isolate equine airways oligomeric mucins, characterize their macromolecular properties, and identify their gene products. To this end, pooled tr...
Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction. Recurrent airway obstruction (RAO) is characterized by neutrophilic airway inflammation and obstruction, and stabling of susceptible horses triggers acute disease exacerbations. Stable dust is rich in endotoxin, which is recognized by Toll-like receptor (TLR) 4. In human bronchial epithelium, TLR4 stimulation leads to elevation of interleukin (IL)-8 mRNA expression. The zinc finger protein A20 negatively regulates this pathway. We hypothesized that TLR4 and IL-8 mRNA and neutrophil numbers are elevated and that A20 mRNA is not increased in RAOs during stabling compared with controls and with R...
Persistent mucus accumulation: a consequence of delayed bronchial mucous cell apoptosis in RAO-affected horses? This study examined the contribution of delayed apoptosis of bronchial mucous cells to mucus accumulation in equine recurrent airway obstruction (RAO). In pilot studies, Bcl-2, an apoptosis inhibitor, was detected in airway mucous cells of RAO-affected horses in remission and during acute disease, when most mucus was secreted. To study whether delayed apoptosis results in an increase in the number of mucous cells during disease recovery, six RAO-affected and six control horses were fed hay for 5 days to induce inflammation and then pellets for 7 days to partially resolve RAO before euthanasia....
Persistent mucin glycoprotein alterations in equine recurrent airway obstruction. Horses with the episodic asthmalike condition of recurrent airway obstruction (RAO) have bouts of inflammation and bronchoconstriction associated with indoor housing. To assess the potential differences in airway secretions between RAO-affected and control horses, methods to quantify mucus secretions were developed and applied to bronchoalveolar lavage fluid. The relative difference in the amount of mucin glycoproteins between control and RAO-affected horses was assessed with a carbohydrate side chain-specific monoclonal antibody (4E4) in an enzyme-linked immunosorbent assay and by carbohydrat...