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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2261. This Article Full Text (PDF) All Versions of this Article: 2002-07-2261v1 101/7/2810    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Radsak, M. P Articles by Schild, H. Search for Related Content PubMed PubMed Citation Articles by Radsak, M. P Articles by Schild, H. Social Bookmarking                   What's this? Submitted July 25, 2002 Accepted November 13, 2002 The heat shock protein Gp96 binds to human neutrophils and monocytes and stimulates effector functions Markus P Radsak, Norbert Hilf, Harpreet Singh-Jasuja, Sibylla Braedel, Peter Brossart, Hans-Georg Rammensee, and Hansjoerg Schild* Department of Hematology/Oncology, University Medical Hospital, Tuebingen, Germany Department of Immunology, Institute for Cell Biology, Tuebingen, Germany * Corresponding author; email: hansjoerg.schild{at}uni-tuebingen.de. The ER-resident heat shock protein Gp96 is involved in protein folding and is released into the extracellular space after necrotic cell death. In this context, Gp96 has immunostimulatory properties: it activates dendritic cells or macrophages and delivers associated peptides into the antigen presentation pathway resulting in the induction of specific T cell responses. The inflammatory response after necrotic tissue damage leads to the recruitment of polymorphonuclear neutrophils (PMN) and monocytes, where they make their first encounter with Gp96. We therefore investigated whether PMN and monocytes interact with Gp96. We were able to show that PMN and monocytes specifically bind FITC-conjugated Gp96. The binding of Gp96-FITC was competed by LPS or fucoidan, a known inhibitor of scavenger receptors. Interestingly, the binding of LPS-FITC was also competed not only by fucoidan, but by Gp96, suggesting that LPS and Gp96 share a common receptor on PMN. One important effector function of PMN is the clearance of an inflammatory site by phagocytosis. We therefore assessed the influence of Gp96 on phagocytic activity using fluorochrome-labeled polystyrene beads. We found a marked enhancement of phagocytosis in the presence of Gp96 and concluded that PMN not only bind Gp96, but are also activated by it. Additionally, Gp96 stimulated PMN and especially monocytes release large amounts of interleukin 8, a potent neutrophil attracting chemokine. In conclusion, we demonstrate that Gp96 specifically binds to and activates PMN and monocytes, extending the function of Gp96 as a danger signal to additional members of the innate immune system. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Osterloh, F. Geisinger, M. Piedavent, B. Fleischer, N. Brattig, and M. Breloer Heat shock protein 60 (HSP60) stimulates neutrophil effector functions J. Leukoc. Biol., August 1, 2009; 86(2): 423 - 434. [Abstract] [Full Text] [PDF] Q.-Q. Huang, R. Sobkoviak, A. R. Jockheck-Clark, B. Shi, A. M. Mandelin II, P. P. Tak, G. K. Haines III, C. V. Nicchitta, and R. M. Pope Heat Shock Protein 96 Is Elevated in Rheumatoid Arthritis and Activates Macrophages Primarily via TLR2 Signaling J. 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