Advanced

Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages.

Soehnlein, Oliver; Kai-Larsen, Ylva; Frithiof, Robert; Sørensen, Ole E LU ; Kenne, Ellinor; Scharffetter-Kochanek, Karin; Eriksson, Einar E; Herwald, Heiko LU ; Agerberth, Birgitta and Lindbom, Lennart (2008) In Journal of Clinical Investigation 118(10). p.3491-3502
Abstract
In acute inflammation, infiltrating polymorphonuclear leukocytes (also known as PMNs) release preformed granule proteins having multitudinous effects on the surrounding environment. Here we present what we believe to be a novel role for PMN-derived proteins in bacterial phagocytosis by both human and murine macrophages. Exposure of macrophages to PMN secretion markedly enhanced phagocytosis of IgG-opsonized Staphylococcus aureus both in vitro and in murine models in vivo. PMN secretion activated macrophages, resulting in upregulation of the Fcgamma receptors CD32 and CD64, which then mediated the enhanced phagocytosis of IgG-opsonized bacteria. The phagocytosis-stimulating activity within the PMN secretion was found to be due to proteins... (More)
In acute inflammation, infiltrating polymorphonuclear leukocytes (also known as PMNs) release preformed granule proteins having multitudinous effects on the surrounding environment. Here we present what we believe to be a novel role for PMN-derived proteins in bacterial phagocytosis by both human and murine macrophages. Exposure of macrophages to PMN secretion markedly enhanced phagocytosis of IgG-opsonized Staphylococcus aureus both in vitro and in murine models in vivo. PMN secretion activated macrophages, resulting in upregulation of the Fcgamma receptors CD32 and CD64, which then mediated the enhanced phagocytosis of IgG-opsonized bacteria. The phagocytosis-stimulating activity within the PMN secretion was found to be due to proteins released from PMN primary granules; thorough investigation revealed heparin-binding protein (HBP) and human neutrophil peptides 1-3 (HNP1-3) as the mediators of the macrophage response to PMN secretion. The use of blocking antibodies and knockout mice revealed that HBP acts via beta(2) integrins, but the receptor for HNP1-3 remained unclear. Mechanistically, HBP and HNP1-3 triggered macrophage release of TNF-alpha and IFN-gamma, which acted in an autocrine loop to enhance expression of CD32 and CD64 and thereby enhance phagocytosis. Thus, we attribute what may be a novel role for PMN granule proteins in regulating the immune response to bacterial infections. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
118
issue
10
pages
3491 - 3502
publisher
American Society for Clinical Investigation
external identifiers
  • WOS:000259828600030
  • PMID:18787642
  • Scopus:55849130745
ISSN
0021-9738
DOI
10.1172/JCI35740
language
English
LU publication?
yes
id
b98a717b-99ef-446a-bf63-b15acc950285 (old id 1243084)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18787642?dopt=Abstract
date added to LUP
2008-10-07 14:21:14
date last changed
2016-12-04 04:39:43
@misc{b98a717b-99ef-446a-bf63-b15acc950285,
  abstract     = {In acute inflammation, infiltrating polymorphonuclear leukocytes (also known as PMNs) release preformed granule proteins having multitudinous effects on the surrounding environment. Here we present what we believe to be a novel role for PMN-derived proteins in bacterial phagocytosis by both human and murine macrophages. Exposure of macrophages to PMN secretion markedly enhanced phagocytosis of IgG-opsonized Staphylococcus aureus both in vitro and in murine models in vivo. PMN secretion activated macrophages, resulting in upregulation of the Fcgamma receptors CD32 and CD64, which then mediated the enhanced phagocytosis of IgG-opsonized bacteria. The phagocytosis-stimulating activity within the PMN secretion was found to be due to proteins released from PMN primary granules; thorough investigation revealed heparin-binding protein (HBP) and human neutrophil peptides 1-3 (HNP1-3) as the mediators of the macrophage response to PMN secretion. The use of blocking antibodies and knockout mice revealed that HBP acts via beta(2) integrins, but the receptor for HNP1-3 remained unclear. Mechanistically, HBP and HNP1-3 triggered macrophage release of TNF-alpha and IFN-gamma, which acted in an autocrine loop to enhance expression of CD32 and CD64 and thereby enhance phagocytosis. Thus, we attribute what may be a novel role for PMN granule proteins in regulating the immune response to bacterial infections.},
  author       = {Soehnlein, Oliver and Kai-Larsen, Ylva and Frithiof, Robert and Sørensen, Ole E and Kenne, Ellinor and Scharffetter-Kochanek, Karin and Eriksson, Einar E and Herwald, Heiko and Agerberth, Birgitta and Lindbom, Lennart},
  issn         = {0021-9738},
  language     = {eng},
  number       = {10},
  pages        = {3491--3502},
  publisher    = {ARRAY(0x9c3b750)},
  series       = {Journal of Clinical Investigation},
  title        = {Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages.},
  url          = {http://dx.doi.org/10.1172/JCI35740},
  volume       = {118},
  year         = {2008},
}