Molecular mechanisms of platelet-mediated leukocyte recruitment during myocardial reperfusion

Leukocyte interaction with platelets and endothelial cells as cause of myocardial stunning was investigated. Mice were anesthetized and, after thoracotomy, the LAD was ligated for 20 min. Where indicated, rhodamine 6G for leukocyte labeling, fluorescence‐labeled platelets, and the GPIIb/IIIa antagon...

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Published in:Journal of leukocyte biology 2002-09, Vol.72 (3), p.455-461
Main Authors: Kupatt, Christian, Wichels, Reinhard, Horstkotte, Jan, Krombach, Fritz, Habazettl, Helmut, Boekstegers, Peter
Format: Article
Language:English
Subjects:
adhesion molecules
Animals
Blood Platelets - drug effects
Blood Platelets - physiology
Cell Adhesion - drug effects
Chemotaxis, Leukocyte - drug effects
Chemotaxis, Leukocyte - physiology
Coronary Vessels
Endothelium, Vascular - pathology
Intercellular Adhesion Molecule-1 - physiology
Ligation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Ischemia - immunology
Myocardial Ischemia - pathology
Myocardial Reperfusion
P-Selectin - physiology
Platelet Adhesiveness - drug effects
Platelet Aggregation Inhibitors - pharmacology
Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex - physiology
PMN
P‐selectin
Tirofiban
Tyrosine - analogs & derivatives
Tyrosine - pharmacology
Ventricular Function, Left
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Summary:Leukocyte interaction with platelets and endothelial cells as cause of myocardial stunning was investigated. Mice were anesthetized and, after thoracotomy, the LAD was ligated for 20 min. Where indicated, rhodamine 6G for leukocyte labeling, fluorescence‐labeled platelets, and the GPIIb/IIIa antagonist Tirofiban wer infused at the onset of reperfusion in vivo. After 15 min, hearts were quickly excised and analyzed by fluorescence microscopy or assessed for left ventricular developed pressure (LVDP). After in vivo ischemia and reperfusion, leukocyte retention in the heart was 55 ± 5/field in wild‐type hearts, 38 ± 3/field in P‐selectin−/− hearts, and 23 ± 4/field in P‐selectin/intercellular adhesion molecule‐1 (ICAM‐1)−/− hearts. Postischemic LVDP (48±4 mmHg in wild‐type hearts) improved in P‐selectin−/− and P‐selectin/ICAM‐1−/− hearts (58±4 and 79±6 mmHg). Tirofiban reduced platelet adhesion (23±4/field vs. 61±2/field in wild‐type hearts) and leukocyte recruitment (34±2/field), improving LVDP (63±4 mmHg). Whereas wild‐type platelets displayed similar adherence to P‐selectin/ICAM‐1−/− hearts as platelets from the same genetic strain (63±3 vs. 61±4 platelets/field), wild‐type platelet infusion restored postischemic leukocyte recruitment in P‐selectin/ICAM‐1−/− hearts (55±4/field vs. 23±4/field), an effect sensitive to Tirofiban inhibition (23±4 leukocytes/field, 22±3 platelets/field). We conclude that platelets contribute postischemic leukocyte adhesion in the heart via P‐selectin and GPIIb/IIIa.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.72.3.455