Distinct inflammatory responses of adherent vascular lung neutrophils to pulmonary irritants.

Abstract

The nature and the extent of the damage that occurs in the lung following exposure to pulmonary irritants vary with the pathogenic agent. In the present studies we determined if this was due to unique functional responses of adherent vascular neutrophils to different irritants. Because of their location within the lung, these cells may be more relevant than circulating neutrophils to the pathophysiology of irritant-induced lung injury. For our studies we used two model irritants, ozone and endotoxin, which cause distinct pathologic effects in the lung. Treatment of rats with ozone resulted in a transient increase (2-fold) in the number of adherent vascular neutrophils in the lung which was maximum 2 hr after exposure and returned to control levels by 12 hr. In contrast, following endotoxin administration, 10-fold greater numbers of adherent neutrophils were recovered from the lung. Moreover, cell number remained elevated 3-fold for up to 48 hr. Unstimulated neutrophils isolated 2-12 hr after endotoxin treatment of rats produced 3 times more superoxide anion than cells from ozone-treated rats. Cells isolated 12-48 hr after endotoxin administration were also sensitized to produce more nitric oxide than cells from ozone-treated rats and to express inducible nitric oxide synthase protein. These data demonstrate that endotoxin and ozone induce distinct patterns of accumulation and functional changes in adherent vascular neutrophils in the lung which may contribute to different pathological processes observed following exposure to these pulmonary irritants.