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CUTTING EDGE |
*
Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division,
Vascular Research Division, Department of Pathology, Brigham and Women’s Hospital, and
Infectious Disease Program, Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
Heat shock proteins (HSP), highly conserved across species, are generally viewed as intracellular proteins thought to serve protective functions against infection and cellular stress. Recently, we have reported the surprising finding that human and chlamydial HSP60, both present in human atheroma, can activate vascular cells and macrophages. However, the transmembrane signaling pathways by which extracellular HSP60 may activate cells remains unclear. CD14, the monocyte receptor for LPS, binds numerous microbial products and can mediate activation of monocytes/macrophages and endothelial cells, thus promoting the innate immune response. We show here that human HSP60 activates human PBMC and monocyte-derived macrophages through CD14 signaling and p38 mitogen-activated protein kinase, sharing this pathway with bacterial LPS. These findings provide further insight into the molecular mechanisms by which extracellular HSP may participate in atherosclerosis and other inflammatory disorders by activating the innate immune system.
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H. Perschinka, M. Mayr, G. Millonig, C. Mayerl, R. van der Zee, S. G. Morrison, R. P. Morrison, Q. Xu, and G. Wick Cross-Reactive B-Cell Epitopes of Microbial and Human Heat Shock Protein 60/65 in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 1060 - 1065. [Abstract] [Full Text] [PDF]
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S. B. Flohe, J. Bruggemann, S. Lendemans, M. Nikulina, G. Meierhoff, S. Flohe, and H. Kolb Human Heat Shock Protein 60 Induces Maturation of Dendritic Cells Versus a Th1-Promoting Phenotype J. Immunol., March 1, 2003; 170(5): 2340 - 2348. [Abstract] [Full Text] [PDF]
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H. Cwiklinska, M. P. Mycko, O. Luvsannorov, B. Walkowiak, C. F. Brosnan, C. S. Raine, and K. W. Selmaj Heat shock protein 70 associations with myelin basic protein and proteolipid protein in multiple sclerosis brains Int. Immunol., February 1, 2003; 15(2): 241 - 249. [Abstract] [Full Text] [PDF]
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B. Gao and M.-F. Tsan Endotoxin Contamination in Recombinant Human Heat Shock Protein 70 (Hsp70) Preparation Is Responsible for the Induction of Tumor Necrosis Factor alpha Release by Murine Macrophages J. Biol. Chem., January 3, 2003; 278(1): 174 - 179. [Abstract] [Full Text] [PDF]
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 J. Campisi and M. Fleshner Role of extracellular HSP72 in acute stress-induced potentiation of innate immunity in active rats J Appl Physiol, January 1, 2003; 94(1): 43 - 52. [Abstract] [Full Text] [PDF]
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K. H. Long, F. J. Gomez, R. E. Morris, and S. L. Newman Identification of Heat Shock Protein 60 as the Ligand on Histoplasma capsulatum That Mediates Binding to CD18 Receptors on Human Macrophages J. Immunol., January 1, 2003; 170(1): 487 - 494. [Abstract] [Full Text] [PDF]
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 J. C. Baker-LePain, M. Sarzotti, T. A. Fields, C.-Y. Li, and C. V. Nicchitta GRP94 (gp96) and GRP94 N-Terminal Geldanamycin Binding Domain Elicit Tissue Nonrestricted Tumor Suppression J. Exp. Med., December 2, 2002; 196(11): 1447 - 1459. [Abstract] [Full Text] [PDF]
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K. Bethke, F. Staib, M. Distler, U. Schmitt, H. Jonuleit, A. H. Enk, P. R. Galle, and M. Heike Different Efficiency of Heat Shock Proteins (HSP) to Activate Human Monocytes and Dendritic Cells: Superiority of HSP60 J. Immunol., December 1, 2002; 169(11): 6141 - 6148. [Abstract] [Full Text] [PDF]
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E. Noessner, R. Gastpar, V. Milani, A. Brandl, P. J. S. Hutzler, M. C. Kuppner, M. Roos, E. Kremmer, A. Asea, S. K. Calderwood, et al. Tumor-Derived Heat Shock Protein 70 Peptide Complexes Are Cross-Presented by Human Dendritic Cells J. Immunol., November 15, 2002; 169(10): 5424 - 5432. [Abstract] [Full Text] [PDF]
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M. Breloer, S. H. More, A. Osterloh, F. Stelter, R. S. Jack, and A. v. Bonin Macrophages as main inducers of IFN-{gamma} in T cells following administration of human and mouse heat shock protein 60 Int. Immunol., November 1, 2002; 14(11): 1247 - 1253. [Abstract] [Full Text] [PDF]
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 A. Shor, P. Libby, P. M. Ridker, and A. Maseri Atherosclerosis: Lipid Infiltration or Chlamydia pneumoniae Infection? * Response Circulation, October 29, 2002; 106 (18): e135 - e136. [Full Text] [PDF]
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Q. Xu Role of Heat Shock Proteins in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1547 - 1559. [Abstract] [Full Text] [PDF]
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B. Billack, D. E. Heck, T. M. Mariano, C. R. Gardner, R. Sur, D. L. Laskin, and J. D. Laskin Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and endothelial cells Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1267 - C1277. [Abstract] [Full Text] [PDF]
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 J C Ranford and B Henderson Chaperonins in disease: mechanisms, models, and treatments Mol. Pathol., August 1, 2002; 55(4): 209 - 213. [Abstract] [Full Text] [PDF]
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