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

• 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
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-06-2559

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.