Increased apoptosis of CD4 and CD8 T lymphocytes in the airways of horses with recurrent airway obstruction

Abstract

Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition similar to human asthma caused by exposure of susceptible horses to poorly ventilated stable environments. The disease is characterized by neutrophilic airway inflammation, mucus hypersecretion and reversible bronchoconstriction. This inflammatory process is mediated by several factors, including antibodies, cytokines, resident cells of the airway and inflammatory cellular components that arrive in the respiratory tract. An increasing body of evidence has lent support to the concept that a dysregulation of T cell apoptosis may play a central role in the development of airway inflammation and the associated asthma. Therefore, the aim of this study was to investigate early and late apoptosis of CD4 and CD8 T cell subpopulations obtained from the airways of acute RAO-positive animals after exposure to hay/straw. The percentages of CD4 and CD8 T cells and their associated frequencies of apoptosis were quantified using flow cytometry. Hay/straw exposure induced clinical airway obstruction, airway neutrophilia and increased airway mucus production in RAO-positive horses. In addition, allergen exposure increased the percentage of CD4 T cells in RAO-positive horses as well as the frequency of early and late apoptosis in both CD4 and CD8 lymphocyte subpopulations. These results suggest that the higher frequency of lymphocyte apoptosis may play a role in disease progression of horses afflicted with RAO and may partially explain the characteristic remission of this pathological condition once the allergen source is removed. However, further studies are needed to clarify the role of T cell apoptosis in RAO-affected horses.

Neutrophil and macrophage apoptosis in bronchoalveolar lavage fluid from healthy horses and horses with recurrent airway obstruction (RAO)

“…An acute crisis of heaves in suitable animals was induced by placing all horses in a poorly ventilated stable, bedding them on straw and feeding them hay with visible mold growth for 48 hours prior to examination. Hay and straw were not shaken up additionally, since the introduction of the horses into the poorly ventilated stable has been shown to suffice in inducing airway inflammation and RAO exacerbation in selected horses [11]. An inflammatory response to the poor environmental conditions was confirmed using a clinical RAO score, an endoscopic examination and bronchoalveolar lavage fluid (BALF) cytology, arterial blood gas analysis and venous blood samplings [13,14].…”

“…Dysregulation of apoptosis has been implicated in a range of diseases including tumors, neurodegenerative and autoimmune disorders, as well as allergic asthma and COPD in humans [6-8]. This process has attracted great attention in horses in recent years, and several studies concerning apoptosis of different lymphocyte subpopulations in RAO-affected horses have been conducted, since delays in the apoptotic response may be associated with persistent inflammation and subsequent tissue damage [9-11]. However, to the authors’ knowledge, only limited research is available concerning the role of cell types other than lymphocytes in RAO affected horses [10,12].…”

Recurrent respiratory disorders in Polish Konik horses - clinical and laboratory findings

“…Breathing problems were exacerbated by placing the horses in poorly ventilated stables, bedding them on poor quality straw, and feeding hay with visible mold growth for 48 h prior to examination. This environment had been previously shown to induce airway inflammation and RAO exacerbation in horses (10).…”

Allergic Airway Inflammation

“…In these animal models, sensitization with various allergens, such as ovalbumin, house dust mite, and aspergillus, induce a phenotype closely resembling that observed in human asthma (Hausding et al 2008;Humar et al 2008;Allen 2009;Bates et al 2009;Qarcoo et al 2009;Moran & Folch 2011). Th2-associated cytokines such as IL-4 are important in driving IgE production to allergens and are essential in the initiation of an allergic airway response (Coyle et al 1995).…”

“…Spinozzi et al (1998) reported that pulmonary T cells isolated from the BALF of atopic asthma patients showed hypoexpression of Fas and FasL; this result may explain the low frequency of apoptosis in this group of patients. In contrast, horses with acute airway allergy have increased apoptosis of airway lymphocytes, which may partially explain the rapid resolution of the pathology once the allergen is removed in this allergy model (Moran et al 2011). However, these authors suggest additional studies to examine apoptosis and cytokine profiles in other stages of the disease.…”