期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 102, 期 3, 页码 763-774出版社
WILEY
DOI: 10.1189/jlb.2MA0117-019R
关键词
chaperone; geldanamycin; PAMPs; phagocytosis; signalling
资金
- National Science Centre (Krakow, Poland) [NN303 8086 40, UMO-2012/05/B/NZ6/00677]
- Polish Ministry of Science and Higher Education
Heat shock proteins (HSPs) are typical intracellular chaperones which also appear on the cell surface and in extracellular milieu. HSP90, which chaperones many proteins involved in signal transduction, is also a regular component of LPS-signaling complexes on M phi. As LPS is a prototypical PAMP, we speculated that HSP90 is engaged in pattern recognition by professional phagocytes. In this report, we provide the first evidence, to our knowledge, of the geldanamycin (Ge)-inhibitable HSP90 on the surface of live monocyte-derived M phi s (hMDMs). Using cytometry and specific Abs, we showed both HSP90 isoforms ( and ) on the surface of human monocytes and hMDMs. The cell-surface HSP90 pool was also labeled with cell-impermeable Ge derivatives. Confocal analysis of hMDMs revealed that HSP90-inhibitor complexes were rapidly clustered on the cell surface and recycled through the endosomal compartment. This finding suggests that the N-terminal (ATPase) domain of HSP90 is exposed and accessible from the extracellular space. To study the role of cell-surface HSP90 in pattern recognition, we used pathogen (PAMPs)- or apoptotic cell-associated molecular patterns (ACAMPs). We showed that blocking the cell-surface HSP90 pool leads to a dramatic decrease in TNF production by monocytes and hMDMs exposed to soluble (TLRs-specific ligands) and particulate [bacteria Staphylococcus aureus (SA) and Porphyromonas gingivalis (PG)] PAMPs. Surprisingly, in hMDMs the functional cell-surface HSP90 was not necessary for the engulfment of either apoptotic neutrophils or bacteria. The presented data suggest that the cell-surface HSP90 is a signaling complex chaperone, with activity that is essential for cytokine response but not for target engulfment by M phi.
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