Heat shock protein 60 (HSP60) stimulates neutrophil effector functions.
Neutrophil granulocytes belong to the first cells that enter sites of infection, where they eliminate infiltrating pathogens via phagocytosis and the release of antimicrobial mediators. Hence, recruitment of neutrophils and activation of neutrophil microbicidal functions are crucial steps in the early containment of infection. In this study, we show that hHSP60 binds to murine and human PMN strongly and specifically. We demonstrate that HSP60 serves as a chemoattractant and modulates neutrophil functions. Human PMN were incubated with HSP60 alone or prior to stimulation with fMLP or PMA acetate. We observed that HSP60, although not inducing neutrophil release of ROS and degranulation itself, strongly enhanced the production of reactive oxygen induced by PMA and the release of primary granule enzymes induced by both secondary stimuli. This sensitization of PMN was HSP60-specific. Moreover, PMN that had been preincubated with HSP60 exhibited a marked increase in the uptake of opsonized Escherichia coli in the absence of additional stimuli. Taken together, our results show for the first time that HSP60 modulates antimicrobial effector functions of neutrophil granulocytes. In this way and in agreement with its function as an endogenous danger signal, HSP60, which is released by damaged tissue, may promote early innate defense mechanisms against invading pathogens.
Osterloh
Anke
A
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. osterloh@bni-hamburg.de
Geisinger
Frank
F
Piédavent
Melanie
M
Fleischer
Bernhard
B
Brattig
Norbert
N
Breloer
Minka
M
D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D005260:Female; D053804:Granzymes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000890:Anti-Infective Agents; D002273:Carcinogens; D018834:Chaperonin 60; D017382:Reactive Oxygen Species; D053804:Granzymes; D013755:Tetradecanoylphorbol Acetate