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PMID: 7512527 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Differential induction of nitric oxide synthase in various organs of the mouse during endotoxaemia: role of TNF-alpha and IL-1-beta.

Immunology ·Vol. 81 ·No. 2 ·1994-02-00 ·Pages 211-5

Cunha FQ, Assreuy J, Moss DW, Rees D, Leal LM, Moncada S, Carrier M, O'Donnell CA, Liew FY

Abstract

BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS) developed lethal septic shock. This was accompanied by significantly elevated concentrations of nitrite and nitrate in the plasma and expression of high levels of nitric oxide (NO) synthase activity in the lungs, heart, spleen and peritoneal macrophages. Mice pretreated with anti-tumour necrosis factor-alpha (TNF-alpha) monoclonal antibody or anti-interleukin-1 beta (IL-1 beta) polyclonal antibody were protected, in a dose-dependent manner, from endotoxin-induced mortality. This effect was accompanied by a significant reduction in plasma levels of nitrite and nitrate. Antibody treatment also reduced the level of NO synthase activity in peritoneal macrophages, spleen and heart but had no effect on enzyme expression in the lung. These results demonstrate that TNF-alpha and IL-1 beta play an important role in the induction of NO following administration of LPS and in the development of endotoxin-induced shock. In addition, NO synthase activity is differentially expressed in various organs and this may not always require TNF-alpha and IL-1 beta.

MeSH Terms
Amino Acid Oxidoreductases/metabolism Animals Endotoxins/blood Escherichia coli Female Interleukin-1/physiology Lipopolysaccharides Lung/enzymology Macrophages, Peritoneal/enzymology Mice Mice, Inbred BALB C Nitric Oxide Synthase Shock, Septic/enzymology Spleen/enzymology Tumor Necrosis Factor-alpha/physiology
Chemicals
Endotoxins Interleukin-1 Lipopolysaccharides Tumor Necrosis Factor-alpha Nitric Oxide Synthase Amino Acid Oxidoreductases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Cunha F Q
Wellcome Research Laboratories, Beckenham, Kent, U.K.
Assreuy J
Moss D W
Rees D
Leal L M
Moncada S
Carrier M
O'Donnell C A
Liew F Y
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Article Info
Journal
Immunology
Abbr.
Immunology
ISSN
0019-2805
Published
1994-02-00
Pages
211-5
Language
English
Region
England
NLM ID
0374672
PMCID
PMC1422329
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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