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P-selectin glycoprotein-ligand-1 regulates pulmonary recruitment of neutrophils in a platelet-independent manner in abdominal sepsis

Muhammad, Asad LU ; Rahman, Milladur LU ; Jeppsson, Bengt LU and Thorlacius, Henrik LU (2009) In British Journal of Pharmacology 156(2). p.307-315
Abstract
Neutrophil-mediated lung injury is an insidious feature in sepsis although the mechanisms regulating pulmonary recruitment of neutrophils remain elusive. Here, we investigated the role of P-selectin glycoprotein-ligand-1 (PSGL-1) in sepsis-induced neutrophil recruitment and tissue injury in the lung. Bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, oedema formation and CXC chemokines were determined 24 h after caecal ligation and puncture (CLP) in mice. Animals were pretreated with a control antibody, monoclonal antibodies directed against PSGL-1 and P-selectin as well as a platelet-depleting antibody directed against GP1b alpha. CLP caused pulmonary damage characterized by oedema formation, neutrophil infiltration... (More)
Neutrophil-mediated lung injury is an insidious feature in sepsis although the mechanisms regulating pulmonary recruitment of neutrophils remain elusive. Here, we investigated the role of P-selectin glycoprotein-ligand-1 (PSGL-1) in sepsis-induced neutrophil recruitment and tissue injury in the lung. Bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, oedema formation and CXC chemokines were determined 24 h after caecal ligation and puncture (CLP) in mice. Animals were pretreated with a control antibody, monoclonal antibodies directed against PSGL-1 and P-selectin as well as a platelet-depleting antibody directed against GP1b alpha. CLP caused pulmonary damage characterized by oedema formation, neutrophil infiltration and increased levels of CXC chemokines in the lung. Immunoneutralization of PSGL-1 or P-selectin reduced CLP-induced neutrophil recruitment in the bronchoalveolar space by more than 56% and lung myeloperoxidase activity by 62%. Notably, the inhibitory effect of the anti-PSGL-1 antibody on sepsis-induced neutrophil infiltration was also observed in platelet-depleted mice. Moreover, inhibition of PSGL-1 and P-selectin abolished CLP-induced oedema formation and tissue damage in the lung. CLP-induced formation of CXC chemokines was not changed in mice pretreated with the anti-PSGL-1 and anti-P-selectin antibodies. These data demonstrate that PSGL-1 plays a key role in pulmonary infiltration of neutrophils as well as lung oedema associated with abdominal sepsis. Moreover, our findings suggest that PSGL-1-dependent neutrophil recruitment is independent of circulating platelets. Thus, these novel findings indicate that PSGL-1 may be a useful target to protect against sepsis-induced accumulation of neutrophils and tissue damage in the lung. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
neutrophil recruitment, lung injury, sepsis
in
British Journal of Pharmacology
volume
156
issue
2
pages
307 - 315
publisher
The British Pharmacological Society
external identifiers
  • wos:000263352000010
  • pmid:19154425
  • scopus:67650222045
ISSN
1476-5381
DOI
10.1111/j.1476-5381.2008.00021.x
language
English
LU publication?
yes
id
ec2d3444-c26c-49e3-92eb-9dc8410a0e3f (old id 1375063)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19154425?dopt=Abstract
date added to LUP
2009-05-08 15:51:47
date last changed
2017-08-20 03:53:23
@article{ec2d3444-c26c-49e3-92eb-9dc8410a0e3f,
  abstract     = {Neutrophil-mediated lung injury is an insidious feature in sepsis although the mechanisms regulating pulmonary recruitment of neutrophils remain elusive. Here, we investigated the role of P-selectin glycoprotein-ligand-1 (PSGL-1) in sepsis-induced neutrophil recruitment and tissue injury in the lung. Bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, oedema formation and CXC chemokines were determined 24 h after caecal ligation and puncture (CLP) in mice. Animals were pretreated with a control antibody, monoclonal antibodies directed against PSGL-1 and P-selectin as well as a platelet-depleting antibody directed against GP1b alpha. CLP caused pulmonary damage characterized by oedema formation, neutrophil infiltration and increased levels of CXC chemokines in the lung. Immunoneutralization of PSGL-1 or P-selectin reduced CLP-induced neutrophil recruitment in the bronchoalveolar space by more than 56% and lung myeloperoxidase activity by 62%. Notably, the inhibitory effect of the anti-PSGL-1 antibody on sepsis-induced neutrophil infiltration was also observed in platelet-depleted mice. Moreover, inhibition of PSGL-1 and P-selectin abolished CLP-induced oedema formation and tissue damage in the lung. CLP-induced formation of CXC chemokines was not changed in mice pretreated with the anti-PSGL-1 and anti-P-selectin antibodies. These data demonstrate that PSGL-1 plays a key role in pulmonary infiltration of neutrophils as well as lung oedema associated with abdominal sepsis. Moreover, our findings suggest that PSGL-1-dependent neutrophil recruitment is independent of circulating platelets. Thus, these novel findings indicate that PSGL-1 may be a useful target to protect against sepsis-induced accumulation of neutrophils and tissue damage in the lung.},
  author       = {Muhammad, Asad and Rahman, Milladur and Jeppsson, Bengt and Thorlacius, Henrik},
  issn         = {1476-5381},
  keyword      = {neutrophil recruitment,lung injury,sepsis},
  language     = {eng},
  number       = {2},
  pages        = {307--315},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {P-selectin glycoprotein-ligand-1 regulates pulmonary recruitment of neutrophils in a platelet-independent manner in abdominal sepsis},
  url          = {http://dx.doi.org/10.1111/j.1476-5381.2008.00021.x},
  volume       = {156},
  year         = {2009},
}