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

Gautam, Narinder; Olofsson, Maria LU ; Herwald, Heiko LU ; Iversen, Lars F.; Lundgren-Åkerlund, Evy; Hedqvist, Per; Arfors, Karl-E.; Flodgaard, Hans and Lindbom, Lennart (2001) In Nature Medicine 7(10). p.1123-1127
Abstract
Polymorphonuclear leukocyte infiltration into tissues in host defense and inflammatory diseasecauses increased vascular permeability and edema formation through unknown mechanisms.Here, we report the involvement of a paracrine mechanism in neutrophil-evoked alteration inendothelial barrier function. We show that upon neutrophil adhesion to the endothelial lining,leukocytic 2 integrin signaling triggers the release of neutrophil-borne heparin-binding protein(HBP), also known as CAP37/azurocidin, a member of the serprocidin family of neutrophilcationic proteins. HBP induced Ca++-dependent cytoskeletal rearrangement and intercellular gapformation in endothelial-cell monolayers in vitro, and increased macromolecular efflux in microvesselsin... (More)
Polymorphonuclear leukocyte infiltration into tissues in host defense and inflammatory diseasecauses increased vascular permeability and edema formation through unknown mechanisms.Here, we report the involvement of a paracrine mechanism in neutrophil-evoked alteration inendothelial barrier function. We show that upon neutrophil adhesion to the endothelial lining,leukocytic 2 integrin signaling triggers the release of neutrophil-borne heparin-binding protein(HBP), also known as CAP37/azurocidin, a member of the serprocidin family of neutrophilcationic proteins. HBP induced Ca++-dependent cytoskeletal rearrangement and intercellular gapformation in endothelial-cell monolayers in vitro, and increased macromolecular efflux in microvesselsin vivo. Moreover, selective inactivation of HBP prevented the neutrophils from inducingendothelial hyperpermeability. Our data suggest a fundamental role of neutrophil-derivedHBP in the vascular response to neutrophil trafficking in inflammation. Targeting this moleculein inflammatory disease conditions offers a new strategy for prevention of endothelial barrierdysfunction caused by misdirected leukocyte activation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
7
issue
10
pages
1123 - 1127
publisher
Nature Publishing Group
external identifiers
  • wos:000171524500033
  • scopus:0034780733
ISSN
1546-170X
DOI
10.1038/nm1001-1123
language
English
LU publication?
yes
id
d797c838-0a21-4730-88b2-e9e46f85d150 (old id 131496)
date added to LUP
2007-07-12 12:48:45
date last changed
2018-10-07 04:23:47
@article{d797c838-0a21-4730-88b2-e9e46f85d150,
  abstract     = {Polymorphonuclear leukocyte infiltration into tissues in host defense and inflammatory diseasecauses increased vascular permeability and edema formation through unknown mechanisms.Here, we report the involvement of a paracrine mechanism in neutrophil-evoked alteration inendothelial barrier function. We show that upon neutrophil adhesion to the endothelial lining,leukocytic 2 integrin signaling triggers the release of neutrophil-borne heparin-binding protein(HBP), also known as CAP37/azurocidin, a member of the serprocidin family of neutrophilcationic proteins. HBP induced Ca++-dependent cytoskeletal rearrangement and intercellular gapformation in endothelial-cell monolayers in vitro, and increased macromolecular efflux in microvesselsin vivo. Moreover, selective inactivation of HBP prevented the neutrophils from inducingendothelial hyperpermeability. Our data suggest a fundamental role of neutrophil-derivedHBP in the vascular response to neutrophil trafficking in inflammation. Targeting this moleculein inflammatory disease conditions offers a new strategy for prevention of endothelial barrierdysfunction caused by misdirected leukocyte activation.},
  author       = {Gautam, Narinder and Olofsson, Maria and Herwald, Heiko and Iversen, Lars F. and Lundgren-Åkerlund, Evy and Hedqvist, Per and Arfors, Karl-E. and Flodgaard, Hans and Lindbom, Lennart},
  issn         = {1546-170X},
  language     = {eng},
  number       = {10},
  pages        = {1123--1127},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Heparin-binding protein (HBP/CAP37): A missing link in neutrophil-evoked alteration of vascular permeability},
  url          = {http://dx.doi.org/10.1038/nm1001-1123},
  volume       = {7},
  year         = {2001},
}