Role of P-Selectin in Platelet Sequestration in Pulmonary Capillaries during Endotoxemia

Abstract

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.

The endothelium in acute lung injury/acute respiratory distress syndrome

“…Platelet P-selectin facilitates platelet-endothelial cell binding [21]. Bound platelets complexed with PMNs release mediators such as TxA 2 and soluble CD40 ligand, leading to endothelial cell and PMN activation, respectively [22 ,23 ].…”

Selectins revisited: the emerging role of platelets in inflammatory lung disease

“…It remains unclear whether platelet P-selectin interacts only with neutrophils or, in addition, also promotes platelet adhesion on lung endothelial cells, which would allow for "secondary capture" of neutrophils to the vascular wall ( Figure 1). Recent intravital microscopic data suggest that activated platelets may attach to lung capillaries via platelet-derived P-selectin (13). This event may even precede the interaction of platelets with neutrophils because intrapulmonary causes of ALI, such as pneumonia or acid aspiration, can be expected to activate the vascular endothelium rather than circulating blood cells (14).…”

Platelets Enhance Endothelial Adhesiveness in High Tidal Volume Ventilation

“…High tidal volume ventilation (HV) causes lung inflammation (1)(2)(3), thereby contributing to morbidity and mortality in acute lung injury (ALI) (4,5) Since it is increasingly evident that activated platelets determine ALI (6)(7)(8), the role of platelets in HV-induced lung inflammation requires further understanding, especially in the context of platelet-endothelial cell (EC) interactions. The EC role is likely to be significant, since inflammatory EC responses, including those relevant to barrier regulation and the expression of proinflammatory receptors, are critical in the development of ALI (4,5,9,10).…”