Role of P-selectin in platelet sequestration in pulmonary capillaries during endotoxemia

Background: There is growing evidence that platelets accumulate in
the lung and contribute to the pathogenesis of acute lung injury
during endotoxemia. The aims of the present study were to localize
platelet sequestration in the pulmonary microcirculation and to
investigate the role of P-selectin as a molecular mechanism of
platelet endothelial cell interaction. Methods: We used in vivo
fluorescence microscopy to quantify the kinetics of fluorescently
labeled erythrocytes and platelets in alveolar capillary networks
in rabbit lungs. Results: Six hours after onset of endotoxin
infusion we observed a massive rolling along and firm adherence of
platelets to lung capillary endothelial cells whereas under control
conditions no platelet sequestration was detected. P-selectin was
expressed on the surface of separated platelets which were
incubated with endotoxin and in lung tissue. Pretreatment of
platelets with fucoidin, a P-selectin antagonist, significantly
attenuated the endotoxin-induced platelet rolling and adherence. In
contrast, intravenous infusion of fucoidin in endotoxin-treated
rabbits did not inhibit platelet sequestration in pulmonary
capillaries. Conclusion: We conclude that platelets accumulate in
alveolar capillaries following endotoxemia. P-selectin expressed on
the surface of platelets seems to play an important role in
mediating this platelet-endothelial cell interaction. Copyright (c)
2006 S. Karger AG, Basel.