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Platelets Enhance Endothelial Adhesiveness in High Tidal Volume Ventilation

¹ Department of Pediatrics, College of Physicians and Surgeons, Columbia University and St. Luke's-Roosevelt Hospital Center, and ² Departments of Pulmonary, Allergy and Critical Care Medicine, College of Physicians and Surgeons, Columbia University, New York, New York; and ³ Department of Pediatrics, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada

Correspondence and requests for reprints should be addressed to Sunita Bhattacharya, M.D., St. Luke's-Roosevelt Hospital Center, AJA #510, 1000 10th Avenue, New York, NY 10019. E-mail: sb80{at}columbia.edu

Although platelets induce lung inflammation, leading to acute lung injury (ALI), the extent of platelet–endothelial cell (EC) interactions remains poorly understood. Here, in a ventilation-stress model of lung inflammation, we show that platelet–EC interactions are important. We obtained freshly isolated lung endothelial cells (FLECs) from isolated, blood-perfused rat lungs exposed to ventilation at low tidal volume (LV) or stress-inducing high tidal volume (HV). Immunofluorescence and immunoprecipitation studies revealed HV-induced increases in cell-surface von Willebrand factor (vWf) expression on FLEC. This increased expression was inhibited by platelet removal from the lung perfusion and by including a P-selectin–blocking antibody in the lung perfusion. The expression was also blocked in lungs from P-selectin knockout (P sel^–/–) mice perfused with autologous blood, but not with heterologous wild-type blood containing P-selectin–expressing platelets. These findings indicate that in ventilation stress, platelets transfer vWf to the EC surface and that platelet P-selectin plays a critical role in this transfer. Further evidence for such intercellular transfers was the HV-induced FLEC expressions of platelet glycoprotein 1b and of platelet P-selectin. We conclude that in ventilation stress, platelets deposit leukocyte- and platelet-binding proteins on the EC surface, thereby establishing the proinflammatory phenotype of the vascular lining.

Key Words: von Willebrand factor • P-selectin • GP1b • lung • platelets

CLINICAL RELEVANCE We show that high tidal volume causes endothelial transfer of platelet vWf and other adhesive proteins, inducing a proinflammatory vascular lining. In addition, the plasma increases of these proteins may underlie distant organ inflammation.

 

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