Heparin-binding protein (HBP/CAP37): A missing link in neutrophil-evoked alteration of vascular perm
Author: ["Narinder Gautam","A. Maria Olofsson","Heiko Herwald","Lars F. Iversen","Evy Lundgren-Åkerlund","Per Hedqvist","Karl-E. Arfors","Hans Flodgaard","Lennart Lindbom"]
Publication: Nature Medicine
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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 β2 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.
Cite this article
Gautam, N., Maria Olofsson, A., Herwald, H. et al. Heparin-binding protein (HBP/CAP37): A missing link in neutrophil-evoked alteration of vascular permeability. Nat Med 7, 1123–1127 (2001). https://doi.org/10.1038/nm1001-1123
