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

Blood 107: 1636-42 (2006)

Speaker: Yu-Tien Chen                        Date: 2006/4/12 13:10~14:00

Commentator: Dr. Chi-Chang Shieh              Place: Room 601

Abstract:

Heat-shock proteins (HSPs) are the most abundant and conserved intracellular proteins in the eukaryotes and prokaryotes. They are involved in multiple essential responses, such as thermotolerance, peptide chaperoning, which are vital for cellular survival.¹ During bacterial and viral infections, lysis of cells releases large amount of host-derived proteins. Amount these proteins, HSPs have been shown to be potent immunoactive agents. ² The authors report here that exogenous HSPs could enhance phagocytosis of macrophages to clear the pathogens; this enhancement was not cause by LPS contamination. They also showed that HSPs could interact with the macrophage membrane lipid rafts, which constitute a platform for signaling transduction and cross-linking of the receptors. Finally, they    found increased T cell proliferation and cytokine secretion after HSPs treatment. These findings suggest a novel mechanism of first-line protection but raise issues by creation of an autoimmune-prone environment, which should be considered before developing clinical applications.

References:

1.          Srivastava, P. K., et al. Roles of heat-shock proteins in innate and adaptive immunity. Nat. Rev. Immunol. 2, 185-94 (2002).

2.          Srivastava, P. K., et al. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int. Immunol. 12, 1539-46 (2000).

3.          Chandawarker, R.Y., et al. Exogenous heat shock protein 70 binds macrophage lipid raft microdomain and stimulates phagocytosis, processing, and MHC-II presentation of antigens. Blood107, 1636-42 (2006).