Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion

Ishikawa, Mami, Cooper, Dianne, Arumugam, Thiruma V., Zhang, John H., Nanda, A and Granger, DN (2004) Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion. Journal of Cerebral Blood Flow and Metabolism, 24 8: 907-915. doi:10.1097/01.WCB.0000132690.96836.7F


Author Ishikawa, Mami
Cooper, Dianne
Arumugam, Thiruma V.
Zhang, John H.
Nanda, A
Granger, DN
Title Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion
Journal name Journal of Cerebral Blood Flow and Metabolism   Check publisher's open access policy
ISSN 0271-678X
1559-7016
Publication date 2004-08
Sub-type Article (original research)
DOI 10.1097/01.WCB.0000132690.96836.7F
Volume 24
Issue 8
Start page 907
End page 915
Total pages 9
Place of publication New York, United States
Publisher Nature Publishing Group
Language eng
Formatted abstract
The adhesion of both leukocytes and platelets to microvascular endothelial cells has been implicated in the pathogenesis of ischemia/reperfusion (I/R) injury in several vascular beds. The objectives of this study were to (1) assess the platelet-leukocyte-endothelial cell interactions induced in the cerebral microvasculature by middle cerebral artery occlusion (MCAO)/reperfusion, and (2) define the molecular determinants of the prothrombogenic and inflammatory responses in this model of focal I/R. MCAO was induced for 1 hour in wild-type (WT) mice, WT mice treated with a monoclonal antibody (mAb) to either P-selectin or GPIIb/IIIa, and in P-selectin-/-(P-sel-/-) chimeras. Isolated platelets labeled with carboxyfluorescein diacetate succinimidyl ester (CFDASE) were administered intravenously and observed with intravital fluorescence microscopy. Leukocytes were observed after intravenous injection of rhodamine 6G. One hour of MCAO followed by 1 hour of reperfusion resulted in the rolling and adhesion of leukocytes in venules, and after 4 hours of reperfusion, the adhesion of both leukocytes and platelets was detected. Although both the P-selectin and GPIIb/IIIa mAbs significantly reduced the adhesion of leukocytes and platelets at 4 hours of reperfusion, the antiadhesive effects of the P-selectin mAb were much greater. The leukocyte and platelet adhesion responses were significantly attenuated in both P-sel-/-right arrowWT and WTright arrowP-sel-/- bone marrow chimeras, compared with WTright arrowWT chimeras. Neutropenia, induced by antineutrophil serum treatment, also reduced the recruitment of leukocytes and platelets after cerebral I/R. These findings implicate a major role for both platelet-associated and endothelial cell-associated P-selectin, as well as neutrophils in the inflammatory and prothrombogenic responses in the microcirculation after focal cerebral I/R.
Keyword Platelet
Leukocyte
P-selectin
GPIIb/IIIa
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 17 Nov 2009, 12:21:41 EST