Document Detail


Hypochlorous acid activates tyrosine phosphorylation signal pathways leading to calcium signaling and TNFalpha production.
MedLine Citation:
PMID:  12215218     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypochlorous acid is an important oxidizing agent produced by neutrophils to aid in defense against pathogens. Although hypochlorous acid is known to cause tissue damage due to its cytotoxicity, the effect of this oxidizing agent on signal transduction by cells of the immune system and its effects on their responses are not well understood. In this study, hypochlorous acid was found to induce cellular tyrosine phosphorylation in both T and B lymphocytes, activate the ZAP-70 tyrosine kinase, and induce cellular calcium signaling in a tyrosine kinase-dependent manner. These signaling events also occurred in T cell lines that did not express the T-cell receptor, indicating the ability of hypochlorous acid to bypass normal receptor control. Hypochlorous acid induced tumor necrosis factor-alpha production in peripheral blood mononuclear cells in a tyrosine kinase-dependent manner. These results suggest that hypochlorous acid may contribute to inflammatory responses by activating signal pathways in cells of the immune system.
Authors:
Gary L Schieven; Henry de Fex; Linda Stephenson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  4     ISSN:  1523-0864     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-09-06     Completed Date:  2003-02-27     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  501-7     Citation Subset:  IM    
Affiliation:
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. gary.schieven@bms.com
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MeSH Terms
Descriptor/Qualifier:
Calcium Signaling / physiology*
Cytokines / metabolism
Enzyme Activation
Enzyme Inhibitors / pharmacology
Humans
Hypochlorous Acid / pharmacology*
Lymphocytes / drug effects*,  immunology
Oxidants / pharmacology*
Phosphorylation
Protein-Tyrosine Kinases / metabolism
Receptors, Antigen, T-Cell / genetics,  metabolism
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / metabolism*
Tyrosine / metabolism*
ZAP-70 Protein-Tyrosine Kinase
Chemical
Reg. No./Substance:
0/Cytokines; 0/Enzyme Inhibitors; 0/Oxidants; 0/Receptors, Antigen, T-Cell; 0/Tumor Necrosis Factor-alpha; 55520-40-6/Tyrosine; 7790-92-3/Hypochlorous Acid; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/ZAP-70 Protein-Tyrosine Kinase; EC 2.7.10.2/ZAP70 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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