The role of neutrophil chemotactic cytokines in the pathogenesis of equine chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is defined as a chronic obstructive inflammatory disease affecting the small airways associated with hay dust exposure (Lowell, F.C., 1964. Observation on heaves. An asthma like syndrome in the horse, J. Allergy 35, 322-330). The disease corresponds histopathologically to a chronic bronchiolitis (Gerber, H., 1973. Chronic pulmonary disease in the horse, Equine Vet. J. 5, 26-33; Winder, N.C., Grünig, G., Hermann, M., Howald, B., von Fellenberg, R., 1989. Comparison of respiratory secretion cytology and pulmonary histology in horses, J. Vet. Med., A36, 32-38) and is mainly characterized by the presence of neutrophil granulocytes in the small bronchioles. Around 12-50% of all horses in Europe and the northern United States suffer from this disease (Mc Pherson, E.A., Lawson, G.H.K., Murphy, J.R., Nicholson, J.M., Fraser, J.A., Breeze, R.G., Pirie, H.M., 1978. Chronic obstructive pulmonary disease (COPD): Identification of affected horses, Eq. Vet. J. 10, 47-53; Larson, V.L., Busch, R.H., 1985. Equine tracheobronchial lavage: Comparison of lavage cytologic features in horses with chronic obstructive pulmonary disease, Am. J. Vet. Res., 46, 144-146; Bracher, V., von Fellenberg, R., Winder, N.C., Grünig, G., 1991. An investigation of the incidence of chronic obstructive pulmonary disease (COPD) in random populations of swiss horses, Equine Vet. J. 23, 136-141). The number of neutrophils in the bronchoalveolar lavage (BAL) and in tracheobronchial secretions (TBS) correlates with the severity of the disease. The present study is focused on the mechanisms which lead to the infiltration of neutrophil granulocytes in the lung of horses. We found that: (1). A strong chemotactic activity in the BAL fluid is associated with high levels of dust exposition. (2). In vitro stimulated alveolar macrophages have impaired phagocytosis efficiency and secrete two chemo-attractants specific for neutrophil granulocytes: Interleukin-8 (IL-8) (Wuyts, A., Proost, P., Put, W., Lenaerts, J.-P., Paemen, L., van Damme, J., 1994. Leucocyte recruitment by monocyte chemotactic proteins (MCPs) secreted by human phagocytes, J. Immunol. Meth. 174, 237-247) and macrophage inflammatory protein-2 (MIP-2) (Wolpe, S.D., Sherry, B., Juers, D., Davatelis, G. Yurt, R.W., Cerami, A., Identification and characterisation of macrophage inflammatory protein-2, Proc. Natl. Acad. Sci. USA 86, 612-616; Tekamp-Olson, P., Gallegos, C., Bauer, D., 1990. Cloning and characterisation of cDNAs for murine macrophage inflammatory protein-2 and its human homologues, J. Exp. Med., 172, 911-927; Driscoll, K.E., 1994. Macrophage inflammatory proteins: Biology and role in pulmonary inflammation. Exp. Lung Res., 20, 473-490). This is associated with the appearance of chemotactic activity in the supernatant. These data confirmed our working hypothesis that bronchiolar neutrophilia may be the consequence of a (over)stimulation of pulmonary macrophages leading to expression of cytokines chemotactic for neutrophil granulocytes.