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Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase.

TitleAltered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase.
Publication TypeJournal Article
Year of Publication1995
AuthorsMacMicking JD, Nathan C, Hom G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N
JournalCell
Volume81
Issue4
Pagination641-50
Date Published1995 May 19
ISSN0092-8674
KeywordsAmino Acid Oxidoreductases, Animals, Bacterial Infections, Base Sequence, Mice, Mice, Mutant Strains, Molecular Sequence Data, Nitric Oxide Synthase, Shock, Septic
Abstract

Mice deficient in inducible nitric oxide synthase (iNOS) were generated to test the idea that iNOS defends the host against infectious agents and tumor cells at the risk of contributing to tissue damage and shock. iNOS-/-mice failed to restrain the replication of Listeria monocytogenes in vivo or lymphoma cells in vitro. Bacterial endotoxic lipopolysaccharide (LPS) caused shock and death in anesthetized wild-type mice, but in iNOS-/-mice, the fall in central arterial blood pressure was markedly attenuated and early death averted. However, unanesthetized iNOS-/-mice suffered as much LPS-induced liver damage as wild type, and when primed with Propionobacterium acnes and challenged with LPS, they succumbed at the same rate as wild type. Thus, there exist both iNOS-dependent and iNOS-independent routes to LPS-induced hypotension and death.

Alternate JournalCell
PubMed ID7538909
Grant ListAI34543 / AI / NIAID NIH HHS / United States
HL51967 / HL / NHLBI NIH HHS / United States

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