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Secretion of heparin-binding protein from human neutrophils is determined by its localization in azurophilic granules and secretory vesicles.

Tapper, Hans LU ; Karlsson, Anna; Mörgelin, Matthias LU ; Flodgaard, Hans and Herwald, Heiko LU (2002) In Blood 99(5). p.1785-1793
Abstract
Human neutrophils have an important role in host defense against microbial infection. At different stages of an infectious process, neutrophils progressively up-regulate receptors and release various effector molecules. These are stored in several distinct types of granules with varying propensity to be secreted. Heparin-binding protein (HBP), also known as CAP37 or azurocidin, is a multifunctional, inactive serine-protease homologue. The present work shows that HBP is released from neutrophils on stimulation with secretagogues that do not trigger the secretion of azurophilic granule content. Therefore, the subcellular localization of HBP was investigated in more detail. Immunofluorescence microscopy revealed that HBP was localized close... (More)
Human neutrophils have an important role in host defense against microbial infection. At different stages of an infectious process, neutrophils progressively up-regulate receptors and release various effector molecules. These are stored in several distinct types of granules with varying propensity to be secreted. Heparin-binding protein (HBP), also known as CAP37 or azurocidin, is a multifunctional, inactive serine-protease homologue. The present work shows that HBP is released from neutrophils on stimulation with secretagogues that do not trigger the secretion of azurophilic granule content. Therefore, the subcellular localization of HBP was investigated in more detail. Immunofluorescence microscopy revealed that HBP was localized close to the plasma membrane. Further analysis by fractionation of postnuclear supernatants from cavitated neutrophils showed that HBP is stored in azurophilic granules and secretory vesicles but that it is also detected to a minor extent in the plasma membrane. These findings were confirmed by immunoelectron microscopy showing that HBP colocalized with marker proteins of azurophilic granules and secretory vesicles. The presence of HBP in secretory vesicles possibly depends on the stage of cell differentiation, since the promyelocytic cell line HL-60 contains less HBP than mature neutrophils, stored exclusively in the less easily mobilized azurophilic granules. Our findings suggest that HBP can be synthesized or targeted to easily mobilized compartments at a late stage of neutrophil maturation. The ability of neutrophils to secrete HBP from secretory vesicles may be important for proinflammatory functions of this protein, such as the alteration of vascular permeability. (Blood. 2002;99:1785-1793) (Less)
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published
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keywords
Neutrophils : metabolism : secretion : ultrastructure, Neutrophil Activation : drug effects, Microscopy Fluorescence, Microscopy Electron, HL-60 Cells, Human, Cytoplasmic Granules : chemistry, Cell Fractionation, Carrier Proteins : agonists : metabolism : secretion, Cell Compartmentation, Support Non-U.S. Gov't, Secretory Vesicles : chemistry, Blood Proteins : agonists : metabolism : secretion, Adult
in
Blood
volume
99
issue
5
pages
1785 - 1793
publisher
American Society of Hematology
external identifiers
  • pmid:11861296
  • wos:000174042700038
  • scopus:0036493524
ISSN
1528-0020
language
English
LU publication?
yes
id
05453352-39a4-4566-84a1-7c11825b6378 (old id 106815)
alternative location
http://bloodjournal.hematologylibrary.org/cgi/content/full/99/5/1785
date added to LUP
2007-07-05 10:26:38
date last changed
2017-12-10 03:46:40
@article{05453352-39a4-4566-84a1-7c11825b6378,
  abstract     = {Human neutrophils have an important role in host defense against microbial infection. At different stages of an infectious process, neutrophils progressively up-regulate receptors and release various effector molecules. These are stored in several distinct types of granules with varying propensity to be secreted. Heparin-binding protein (HBP), also known as CAP37 or azurocidin, is a multifunctional, inactive serine-protease homologue. The present work shows that HBP is released from neutrophils on stimulation with secretagogues that do not trigger the secretion of azurophilic granule content. Therefore, the subcellular localization of HBP was investigated in more detail. Immunofluorescence microscopy revealed that HBP was localized close to the plasma membrane. Further analysis by fractionation of postnuclear supernatants from cavitated neutrophils showed that HBP is stored in azurophilic granules and secretory vesicles but that it is also detected to a minor extent in the plasma membrane. These findings were confirmed by immunoelectron microscopy showing that HBP colocalized with marker proteins of azurophilic granules and secretory vesicles. The presence of HBP in secretory vesicles possibly depends on the stage of cell differentiation, since the promyelocytic cell line HL-60 contains less HBP than mature neutrophils, stored exclusively in the less easily mobilized azurophilic granules. Our findings suggest that HBP can be synthesized or targeted to easily mobilized compartments at a late stage of neutrophil maturation. The ability of neutrophils to secrete HBP from secretory vesicles may be important for proinflammatory functions of this protein, such as the alteration of vascular permeability. (Blood. 2002;99:1785-1793)},
  author       = {Tapper, Hans and Karlsson, Anna and Mörgelin, Matthias and Flodgaard, Hans and Herwald, Heiko},
  issn         = {1528-0020},
  keyword      = {Neutrophils : metabolism : secretion : ultrastructure,Neutrophil Activation : drug effects,Microscopy Fluorescence,Microscopy Electron,HL-60 Cells,Human,Cytoplasmic Granules : chemistry,Cell Fractionation,Carrier Proteins : agonists : metabolism : secretion,Cell Compartmentation,Support Non-U.S. Gov't,Secretory Vesicles : chemistry,Blood Proteins : agonists : metabolism : secretion,Adult},
  language     = {eng},
  number       = {5},
  pages        = {1785--1793},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Secretion of heparin-binding protein from human neutrophils is determined by its localization in azurophilic granules and secretory vesicles.},
  volume       = {99},
  year         = {2002},
}