Exogenous heat shock protein 70 binds macrophage lipid raft microdomain and stimulates phagocytosis, processing, and MHC-II presentation of antigens

The extracellular presence of endotoxin-free heat shock protein 70 (HSP70) enhances the rate and capacity of macrophage-mediated phagocytosis at 6 times the basal rate. It is protein-specific, dose- and time-dependent and involves the internalization of inert microspheres, Gram-positive and -negativ...

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Bibliographic Details
Published in:Blood 2006-02, Vol.107 (4), p.1636-1642
Main Authors: Wang, Ruibo, Kovalchin, Joseph T., Muhlenkamp, Peggy, Chandawarkar, Rajiv Y.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Histocompatibility Antigens Class II - genetics
HSP70 Heat-Shock Proteins - pharmacology
Humans
Immunobiology
Major Histocompatibility Complex
Membrane Microdomains - drug effects
Membrane Microdomains - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Monocytes, macrophages
Myeloid cells: ontogeny, maturation, markers, receptors
Phagocytes - drug effects
Phagocytes - immunology
Phagocytes - physiology
Phagocytosis - drug effects
Phagocytosis - physiology
Receptors, Antigen, T-Cell, alpha-beta - genetics
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Summary:The extracellular presence of endotoxin-free heat shock protein 70 (HSP70) enhances the rate and capacity of macrophage-mediated phagocytosis at 6 times the basal rate. It is protein-specific, dose- and time-dependent and involves the internalization of inert microspheres, Gram-positive and -negative bacteria and fungi. Structurally, exogenous HSP70 binds the macrophage plasma membrane, specifically on its lipid raft-microdomain. Disruption of lipid rafts, HSP70-LR interaction, or denaturing HSP70 abrogates the HSP-mediated increase in phagocytosis. Further, HSP70-mediated phagocytosis directly enhances the processing and presentation of internalized antigens via the endocytic MHC class-II pathway to CD4+ T lymphocytes. Modulating the HSP70-LR interaction presents an opportunity to intervene at the level of host-pathogen interface: a therapeutic tool for emerging infections, especially when conventional treatment with antibiotics is ineffective (antibiotic resistance) or unavailable (rapidly spreading, endemic). These results identify a new role for HSP70, a highly conserved molecule in stimulating phagocytosis: a primordial macrophage function, thereby influencing both innate and adaptive immune responses.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-06-2559