Pulmonary alveolar macrophage function during acute inflammatory lung injury.
Pulmonary alveolar macrophages (PAM) are present during acute lung inflammation, yet the functional role of these cells in both the initiation and resolution of lung injury is not well defined. To better understand the relationship between PAM functional responses and the evolution of acute reversible lung injury, we examined the ability of both unstimulated and stimulated (PMA, zymosan) PAM to secrete reactive oxygen metabolites (superoxide anion O2-) and lysosomal enzymes (lysozyme, N-acetyl-B-D-glucosaminidase) at specific time points (0, 6, 12, 24, 48, and 72 h) after initiation of acute lung injury via reverse passive Arthus reaction in pathogen-free Sprague-Dawley rats. After acute lung injury, stimulated PAM produced increasing amounts of O2- compared with PAM from noninjured lungs. Maximal O2- production by PAM occurred at 24 h after lung injury, at which time a 3.5-fold and 50% increase in O2- production by PAM was observed when PAM were stimulated with PMA and zymosan, respectively. The amount of O2- generated by these cells slowly decreased during the next 48 h. Enhanced generation of O2- by PAM from injured lungs was not due to altered enzymatic activity of the O2--producing NADPH oxidase, nor was it due to an absolute increase in the NADPH oxidase in "activated" PAM. These observations suggest that increased O2- generation by PAM from injured lungs is due to enhancement of mechanisms responsible for induction of oxidase activity. In addition, a differential accumulation and secretion of lysozyme and N-acetyl-B-D-glucosaminidase activity by PAM was observed after acute lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)
D000210:Acute-Phase Reaction / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002452:Cell Count; D007111:Immunity, Cellular; D007249:Inflammation / Q000503:physiopathology*; D007700:Kinetics; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D011506:Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism
D011506:Proteins; D013481:Superoxides