Platelet-endothelial cell interaction in pulmonary micro-circulation: the role of PARS.
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.
Kiefmann
Rainer
R
Department of Anesthesiology, Ludwig Maximilians University, Marchioninistr. 15, 81377 Munich, Germany.
Heckel
Kai
K
Schenkat
Sonja
S
Dörger
Martina
M
Wesierska-Gadek
Józefa
J
Goetz
Alwin E
AE
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D019446:Endotoxemia / Q000097:blood; D007249:Inflammation / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000473:pathology; D018715:Microscopy, Video; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*; D011652:Pulmonary Circulation; D011817:Rabbits; D019087:Selectins / Q000502:physiology
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019087:Selectins; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases