TY - JOUR
T1 - Molecular mechanisms of platelet-mediated leukocyte recruitment during myocardial reperfusion
AU - Kupatt, Christian
AU - Wichels, Reinhard
AU - Horstkotte, Jan
AU - Krombach, Fritz
AU - Habazettl, Helmut
AU - Boekstegers, Peter
PY - 2002/9/1
Y1 - 2002/9/1
N2 - 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 were 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 wildtype 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.
AB - 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 were 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 wildtype 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.
KW - Adhesion molecules
KW - P-selectin
KW - PMN
KW - Tirofiban
UR - http://www.scopus.com/inward/record.url?scp=0036744003&partnerID=8YFLogxK
M3 - Article
C2 - 12223512
AN - SCOPUS:0036744003
SN - 0741-5400
VL - 72
SP - 455
EP - 461
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -