title: Hsp70 and cardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects.
abstract: Open heart surgery is a unique model to study the interplay between cellular injury, regulation of inflammatory responses and tissue repair. Stress-inducible heat shock protein 70-kDa (Hsp70) provides a molecular link between these events. In addition to molecular chaperoning, Hsp70 exerts modulatory effects on endothelial cells and leukocytes involved in inflammatory networks. Hsp70 residing in the intracellular compartment is part of an inhibitory feedback loop that acts on nuclear factor kappaB (NF-kappaB). In contrast, extracellular Hsp70 is recognized by multiple germline-encoded immune receptors, e.g., Toll-like receptor (TLR) 2, TLR4, LOX-1, CD91, CD94, CCR5 and CD40. Hsp70 is thereby able to enhance chemotaxis, phagocytosis and cytolytic activity of innate immune cells and stimulate antigen-specific responses. These apparent contradictory pro- and anti-inflammatory effects of endogenous Hsp70 in the context of cardiac surgery are still not fully understood. An all-embracing model of the compartmentalized effects of endogenous Hsp70 in the orchestration of inflammatory responses in cardiac surgery is proposed.
authors.affiliation: Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Petrus R
authors.initials: PR
authors.lastname: de Jong
authors.forename: Alvin W L
authors.initials: AW
authors.lastname: Schadenberg
authors.forename: Nicolaas J G
authors.initials: NJ
authors.lastname: Jansen
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
mesh_terms: D000818:Animals; D006348:Cardiac Surgical Procedures; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism*; D007700:Kinetics; D016328:NF-kappa B / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B