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P-selectin glycoprotein-ligand-1 regulates pulmonary recruitment of neutrophils in a platelet-independent manner in abdominal sepsis
- Source :
- British Journal of Pharmacology. 156:307-315
- Publication Year :
- 2009
- Publisher :
- Wiley, 2009.
-
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.
- Subjects :
- Blood Platelets
Male
Pathology
medicine.medical_specialty
P-selectin
Neutrophils
Pulmonary Edema
Lung injury
Sepsis
Mice
Abdomen
medicine
Animals
Lung
Peroxidase
Pharmacology
Membrane Glycoproteins
integumentary system
biology
business.industry
Respiratory disease
Lung Injury
respiratory system
medicine.disease
Pulmonary edema
Mice, Inbred C57BL
medicine.anatomical_structure
Neutrophil Infiltration
Myeloperoxidase
Immunology
biology.protein
business
Chemokines, CXC
Infiltration (medical)
Research Paper
Subjects
Details
- ISSN :
- 14765381 and 00071188
- Volume :
- 156
- Database :
- OpenAIRE
- Journal :
- British Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....c6f9bdaafa4605fa5a1f69509117e7cb