Document Detail


Induction of intracellular arginase activity does not diminish the capacity of macrophages to produce nitric oxide in vitro.
MedLine Citation:
PMID:  10416126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The hypothesis was tested that induction of arginase expression in macrophages (M phi) diminishes nitric oxide (NO) synthesis due to intracellular competition between arginase and inducible nitric oxide synthase (iNOS) for L-arginine (L-arg). Murine M phi cell lines and bone marrow-derived M phi (BMM) were stimulated to express either iNOS or arginase or to co-express these two enzymes. The response pattern obtained was complex but allowed the following conclusions: (i) iNOS and arginase are differentially regulated. (ii) High intracellular arginase levels do not limit the capacity of M phi to synthesize NO even when the L-arg concentration in the culture medium is lowered to physiological levels. (iii) Arginase levels in BMM pre-exposed to either M phi colony-stimulating factor (M-CSF) or granulocyte-M phi colony-stimulating factor (GM-CSF) differ markedly, but iNOS expression and NO synthesis by the two BMM types is similar. (iv) Regulation of iNOS and arginase differs between primary murine bone marrow M phi and murine M phi cell lines. (v) Arginase activity appears to be inhibited during high-output NO synthesis. Taken together, our results show that NO production by M phi is not compromised by conditions that increase intracellular arginase activity.
Authors:
J Fligger; J Blum; T W Jungi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunobiology     Volume:  200     ISSN:  0171-2985     ISO Abbreviation:  Immunobiology     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-10-07     Completed Date:  1999-10-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8002742     Medline TA:  Immunobiology     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  169-86     Citation Subset:  IM    
Affiliation:
Institute of Veterinary Virology, University of Berne, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginase / biosynthesis*
Arginine / pharmacology
Bone Marrow Cells
Cell Line
Dose-Response Relationship, Drug
Enzyme Induction
Macrophages / drug effects,  enzymology*
Mice
Nitric Oxide / biosynthesis
Nitric Oxide Synthase / biosynthesis*
Nitric Oxide Synthase Type II
Urea / metabolism
Chemical
Reg. No./Substance:
10102-43-9/Nitric Oxide; 57-13-6/Urea; 74-79-3/Arginine; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse; EC 3.5.3.1/Arginase

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