P-selectin glycoprotein-ligand-1 regulates pulmonary recruitment of neutrophils in a platelet-independent manner in abdominal sepsis
Autor: | Henrik Thorlacius, Muhammad Asaduzzaman, Milladur Rahman, Bengt Jeppsson |
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Rok vydání: | 2009 |
Předmět: |
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 |
Zdroj: | British Journal of Pharmacology. 156:307-315 |
ISSN: | 1476-5381 0007-1188 |
Popis: | 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. |
Databáze: | OpenAIRE |
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