Susceptibility to ozone-induced acute lung injury in iNOS-deficient mice.
Mice deficient in inducible nitric oxide synthase (iNOS; C57Bl/6Ai-[KO]NOS2 N5) or wild-type C57Bl/6 mice were exposed to 1 part/million of ozone 8 h/night or to filtered air for three consecutive nights. Endpoints measured included lavagable total protein, macrophage inflammatory protein (MIP)-2, matrix metalloproteinase (MMP)-9, cell content, and tyrosine nitration of whole lung proteins. Ozone exposure caused acute edema and an inflammatory response in the lungs of wild-type mice, as indicated by significant increases in lavage protein content, MIP-2 and MMP-9 content, and polymorphonuclear leukocytes. The iNOS knockout mice showed significantly greater levels of lung injury by all of these criteria than did the wild-type mice. We conclude that iNOS knockout mice are more susceptible to acute lung damage induced by exposure to ozone than are wild-type C57Bl/6 mice and that protein nitration is associated with the degree of inflammation and not dependent on iNOS-derived nitric oxide.
Kenyon
Nicholas J
NJ
Pulmonary/Critical Care Medicine, School of Medicine, University of California, Davis, California 95616-8723, USA.
van der Vliet
Albert
A
Schock
Bettina C
BC
Okamoto
Tatsuya
T
McGrew
Gabrielle M
GM
Last
Jerold A
JA
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D004198:Disease Susceptibility; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009504:Neutrophils / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010126:Ozone; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D011506:Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D010126:Ozone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020780:Matrix Metalloproteinase 9