title: Platelets enhance endothelial adhesiveness in high tidal volume ventilation.
abstract: 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.
authors.affiliation: Department of Pediatrics, College of Physicians and Surgeons, Columbia University and St Luke's-Roosevelt Hospital Center, New York, NY 10019, USA.
authors.forename: Maimaiti T
authors.initials: MT
authors.lastname: Yiming
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Alice
authors.initials: A
authors.lastname: Huertas
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Issekutz
authors.forename: Sunita
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism*; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006612:High-Frequency Ventilation; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019007:P-Selectin; D014841:von Willebrand Factor