P‐selectin glycoprotein‐ligand‐1 regulates pulmonary recruitment of neutrophils in a platelet‐independent manner in abdominal sepsis
Open Access
- 1 January 2009
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 156 (2), 307-315
- https://doi.org/10.1111/j.1476-5381.2008.00021.x
Abstract
Background and purpose: 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. Experimental approach: 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 GP1bα. Key results: 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. Conclusions and implications: 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.Keywords
This publication has 47 references indexed in Scilit:
- Guide to Receptors and Channels (GRAC), 3rd editionBritish Journal of Pharmacology, 2008
- Platelet‐dependent accumulation of leukocytes in sinusoids mediates hepatocellular damage in bile duct ligation‐induced cholestasisBritish Journal of Pharmacology, 2008
- Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregationJCI Insight, 2006
- Neutrophil Cytoskeletal Rearrangements during Capillary Sequestration in Bacterial Pneumonia in RatsAmerican Journal of Respiratory and Critical Care Medicine, 2006
- Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortalityThe Journal of Experimental Medicine, 2006
- Immunoblockade of PSGL-1 attenuates established experimental murine colitis by reduction of leukocyte rollingAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2004
- Platelet P-selectin facilitates atherosclerotic lesion developmentBlood, 2003
- Sequential observation of micrometastasis formation by bacterial lacZ gene-tagged Lewis lung carcinoma cellsCancer Letters, 1997
- Mast Cell Activation Induces P-Selectin-Dependent Leukocyte Rolling and Adhesion in Postcapillary Venules in VivoBiochemical and Biophysical Research Communications, 1994
- Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigmCell, 1994