title: Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability.
abstract: Polymorphonuclear leukocyte infiltration into tissues in host defense and inflammatory disease causes increased vascular permeability and edema formation through unknown mechanisms. Here, we report the involvement of a paracrine mechanism in neutrophil-evoked alteration in endothelial barrier function. We show that upon neutrophil adhesion to the endothelial lining, leukocytic beta2 integrin signaling triggers the release of neutrophil-borne heparin-binding protein (HBP), also known as CAP37/azurocidin, a member of the serprocidin family of neutrophil cationic proteins. HBP induced Ca++-dependent cytoskeletal rearrangement and intercellular gap formation in endothelial-cell monolayers in vitro, and increased macromolecular efflux in microvessels in vivo. Moreover, selective inactivation of HBP prevented the neutrophils from inducing endothelial hyperpermeability. Our data suggest a fundamental role of neutrophil-derived HBP in the vascular response to neutrophil trafficking in inflammation. Targeting this molecule in inflammatory disease conditions offers a new strategy for prevention of endothelial barrier dysfunction caused by misdirected leukocyte activation.
authors.affiliation: Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Gautam
authors.forename: A M
authors.initials: AM
authors.lastname: Olofsson
authors.forename: H
authors.initials: H
authors.lastname: Herwald
authors.forename: L F
authors.initials: LF
authors.lastname: Iversen
authors.forename: E
authors.initials: E
authors.lastname: Lundgren-Akerlund
authors.forename: P
authors.initials: P
authors.lastname: Hedqvist
authors.forename: K E
authors.initials: KE
authors.lastname: Arfors
authors.forename: H
authors.initials: H
authors.lastname: Flodgaard
authors.forename: L
authors.initials: L
authors.lastname: Lindbom
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*
chemical_list: C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D002118:Calcium