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.


CONCLUSIONS
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.
Kiefmann
Rainer
R
Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Heckel
Kai
K
Schenkat
Sonja
S
Dörger
Martina
M
Goetz
Alwin Eduard
AE
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002196:Capillaries / Q000503:physiopathology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood / Q000503:physiopathology*; D004912:Erythrocytes / Q000502:physiology; D007700:Kinetics; D019007:P-Selectin / Q000097:blood / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology*; D011817:Rabbits
D019007:P-Selectin