Alveolar fibrosis and changes in equine lung morphometry in response to intrapulmonary blood.

Abstract

Necropsy studies of horses suffering exercise-induced pulmonary haemorrhage (EIPH) have identified mild inflammatory lesions with evidence of alveolar fibrosis and bronchiolitis. These lesions were thought to be the result of viral infections that predisposed the affected regions of the lung to EIPH. We have shown previously that during erythrophagocytosis in the alveolar space, there is a prolonged period of macrophage influx and activation. This present study used morphometric analysis to quantify the effects of macrophage activity during erythrophagocytosis, on the alveolar cell population and physical structure of the alveolar walls. Segments of the bronchial tree were inoculated with either autologous whole blood or serum, at 15, 8, 3 days, 24 h and 30 min prior to euthanasia. Blood inoculation produced many significant changes in the alveolar morphometry including, increased numbers of alveolar macrophages, increased septal thickness, and a markedly increased percentage of collagen in the alveolar walls. Signs of chronic inflammation including increased macrophage activity and erythrophagocytosis coincided with increased alveolar macrophage numbers (10,688 +/- 1708 cells/mm3 to 30,957 +/- 6831 cells/mm3), septal thickness (4.1 +/- 0.4 microm to 6.1 +/- 0.5 microm) and alveolar septal collagen content (6.6 +/- 0.5% to 27.5 +/- 3.3%). The results suggest that intrapulmonary blood induces a macrophage dominated inflammatory response, septal thickening and the development of alveolar fibrosis. These changes are the probable cause of the observed alveolar fibrosis and bronchiolitis that was once suspected to be the originating cause of EIPH.