Heat Shock Proteins gp96 and hsp70 Activate the Release of Nitric Oxide by APCs

NO is a cytotoxic and immunomodulatory cytokine produced by macrophages and dendritic cells. We show that stimulation of murine and human macrophages with the heat shock proteins gp96 and hsp70 results in induction of inducible NO synthase and the production of NO. The release of NO by monocytes exp...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 168; no. 6; pp. 2997 - 3003
Main Authors:	Panjwani, Naveed N, Popova, Lana, Srivastava, Pramod K
Format:	Journal Article
Language:	English
Published:	United States Am Assoc Immnol 15-03-2002
Subjects:	Animals Antigen-Presenting Cells - enzymology Antigen-Presenting Cells - metabolism Antigens, Neoplasm - physiology Cell Communication - immunology Cell Differentiation - immunology Cell Line Dendritic Cells - cytology Dendritic Cells - metabolism Drug Synergism Enzyme Induction - immunology Female glycoprotein gp96 HSP70 Heat-Shock Proteins - physiology Hsp70 protein Humans Interferon-gamma - physiology Macrophages, Peritoneal - enzymology Macrophages, Peritoneal - metabolism Membrane Glycoproteins - physiology Mice Mice, Inbred C57BL Nitric Oxide - metabolism Nitric Oxide Synthase - biosynthesis Nitric Oxide Synthase Type II U937 Cells
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Summary:	NO is a cytotoxic and immunomodulatory cytokine produced by macrophages and dendritic cells. We show that stimulation of murine and human macrophages with the heat shock proteins gp96 and hsp70 results in induction of inducible NO synthase and the production of NO. The release of NO by monocytes exposed to hsp60 has been documented previously. Immature, but not mature, dendritic cells respond in the same manner. The activity of heat shock proteins is relatively unaffected by an antagonist of LPS, and is abrogated by heat denaturation. Macrophages have been shown previously to produce NO in response to stimulation with IFN-gamma; stimulation of macrophages with mixtures of IFN-gamma and gp96 or hsp70 leads to a synergistic production of NO. The present observations extend the roles of these heat shock proteins in innate immune responses to another potent and highly conserved function of APC.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.168.6.2997