title: Stress proteins and initiation of immune response: chaperokine activity of hsp72.
abstract: From its original description as solely an intracellular molecular chaperone, heat shock proteins have now been shown to function as initiators of the host's immune response. Although the exact mechanism by which intracellular heat shock proteins leave cells is still incompletely understood, recent work from several labs suggest that heat shock proteins are released by both passive (necrotic) and active (physiological) mechanisms. Binding to specific surface receptors is a prerequisite for the initiation of an immune response. To date, several cell surface proteins have been described as the receptor for seventy kilo-Dalton heat shock protein (Hsp70) including Toll-like receptors 2 and 4 with their cofactor CD14, the scavenger receptor CD36, the low-density lipoprotein receptor-related protein CD91, the C-type lectin receptor LOX-1, and another member of the scavenger super-family SR-A plus the co-stimulatory molecule, CD40. Binding of Hsp70 to these surface receptors specifically activates intracellular signaling cascades, which in turn exert immunoregulatory effector functions; a process known as the chaperokine activity of Hsp70. This review will highlight recent advances in understanding the mechanism by which Hsp70 initiates the host's immune response.
authors.affiliation: Division of Investigative Pathology, Scott & White Clinic and The Texas A&M University System Health Science Center College of Medicine, Temple 76508, USA. asea@medicine.tamhsc.edu
authors.forename: Alexzander
authors.initials: A
authors.lastname: Asea
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D007109:Immunity; D008954:Models, Biological; D018832:Molecular Chaperones / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004731:Endotoxins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011956:Receptors, Cell Surface