Platelet-endothelial cell interaction in pulmonary microcirculation: the role of PARS

Rainer Kiefmann; Kai Heckel; Sonja Schenkat; Martina Dörger; Józefa Węsierska-Gądek; Alwin E. Goetz

doi:10.1160/TH03-11-0685

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(04): 761-770
DOI: 10.1160/TH03-11-0685

Platelets and Blood Cells

Schattauer GmbH

Platelet-endothelial cell interaction in pulmonary microcirculation: the role of PARS

Rainer Kiefmann

¹Department of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany

,

Kai Heckel

¹Department of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany

,

Sonja Schenkat

²Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany

,

Martina Dörger

²Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany

,

Józefa Węsierska-Gądek

³Institute for Cancer Research, University of Vienna, Vienna, Austria

,

Alwin E. Goetz

¹Department of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany

› Author Affiliations

Abstract

Summary

Accumulation of platelets might contribute to acute lung injury during systemic inflammation. The aim of the study was to elucidate the role of the poly (ADP-ribose) synthetase, a nucleotide-polymerizising enzyme, in mediation of platelet-endothelial cell interaction through regulation of adhesion molecules within the pulmonary microcirculation during endotoxemia. We used in vivo fluorescence microscopy to quantify kinetics of fluorescently labeled erythrocytes and platelets in rabbit pulmonary arterioles and venules. Six hours after onset of endotoxin infusion we observed a massive interaction of platelets with the microvascular endothelial cells, whereas under control conditions, no platelet sequestration was measured. An up-regulation of P- and E-selectin was detected in lung tissue following endotoxin infusion by immunohistochemistry and Western blot analysis. Blockade of endothelial P-selectin with fucoidin resulted in a reduction of the endotoxin-induced platelet-endothelial cell interaction. Inhibition of poly (ADP-ribose) synthetase by 3-aminobenzamide inhibited the endotoxin-induced expression of endothelial P- and E-selectin and the subsequent recruitment of platelets. In summary, we provide first in vivo evidence that platelets accumulate in pulmonary microcirculation following endotoxemia. Poly (ADP-ribose) synthetase seems to mediate this platelet-endothelial cell interaction via P- and E-selectin expressed on the surface of microvascular endothelium.

Keywords

Acute lung injury - poly (ADP-ribose) synthetase (PARS) - in vivo fluorescence intravital microscopy - thrombocytes - P- and E-selectin

Full Text

References

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