The role of neutrophils, oxidants, and proteases in the pathogenesis of acid pulmonary injury.
We recently reported a biphasic injury pattern of nonlethal acid aspiration pneumonitis in rats. The first phase consisted of the immediate effects of the direct tissue injury, and the second phase was associated with a neutrophilic inflammatory response. Using this model, the present report examines the possible role of neutrophils, oxidants, and proteases in the pathogenesis of the second phase of this lung injury. Acid aspiration injury was induced by instillation of saline/HCl, pH = 1.25, into the trachea of rats. Lung injury was assessed by measuring the degree of alveolar capillary permeability to 125I-labeled albumin (permeability index [PI]). Rats made neutropenic with polyclonal antineutrophil antibody had a lower PI (0.44 +/- 0.07, P less than 0.05) 6 h after acid aspiration than similarly injured animals with normal whole blood neutrophil counts (PI = 0.85 +/- 0.03). Even though neutrophils appeared necessary for the full development of the lung injury in this model, the administration of different intravenous and/or intratracheal concentrations of either deferoxamine or catalase offered no protection against injury. This suggests that neutrophil oxidants were minimally involved in the injury. Large increases in leukocyte-free serine protease activity (1,477 +/- 438 u/ml, P less than 0.05) were detected in the bronchoalveolar lavage fluid from the saline/HCl, pH = 1.25, injured rats at 6 h postinjury, as compared to saline/HCl, pH = 5.3, treated control animals (2.7 +/- 0.2 u/ml). This study supports the hypothesis that neutrophils are necessary for the full expression of acid-induced lung injury and that the generation of leukocyte-derived oxidants does not appear to be the primary mechanism involved in this injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Knight
P R
PR
Department of Anesthesiology, University of Michigan Medical School, Ann Arbor.
Druskovich
G
G
Tait
A R
AR
Johnson
K J
KJ
D000818:Animals; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D016877:Oxidants / Q000633:toxicity*; D011015:Pneumonia, Aspiration / Q000209:etiology*; D051381:Rats; D012697:Serine Endopeptidases / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms
D016877:Oxidants; D012697:Serine Endopeptidases