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 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.
Panjwani
Naveed N
NN
Cellular and Molecular Immunology Group, Antigenics, Inc., Woburn, MA 01801. Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030.
Popova
Lana
L
Srivastava
Pramod K
PK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D004357:Drug Synergism; D004790:Enzyme Induction / Q000276:immunology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D020298:U937 Cells
D000951:Antigens, Neoplasm; D018840:HSP70 Heat-Shock Proteins; D008562:Membrane Glycoproteins; C052646:sarcoma glycoprotein gp96 rejection antigens; D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse