Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability

Nat Med. 2001 Oct;7(10):1123-7. doi: 10.1038/nm1001-1123.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides
  • Blood Proteins / metabolism*
  • Blood Proteins / pharmacology
  • Calcium / metabolism
  • Capillary Permeability / physiology*
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Cattle
  • Cell Membrane Permeability
  • Cells, Cultured
  • Cytoskeleton / physiology
  • Endothelium, Vascular / cytology
  • Humans
  • Neutrophils / metabolism*


  • AZU1 protein, human
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Carrier Proteins
  • Calcium