Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor gamma-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury.
Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor gamma-chain (FcR gamma) is coexpressed with glycoprotein (GP) VI, forming a platelet collagen receptor, and the activation of platelets by collagen is closely coupled with tyrosine phosphorylation of the FcRgamma. To examine the functional significance of platelet FcR gamma/GPVI complex in the early phase of myocardial ischemia and reperfusion injury in mice, we performed coronary occlusion and reperfusion experiments using wild type mice and FcRgamma-deficient (FcRgamma(-/-)) mice that lack GPVI. The infarct size was significantly smaller in FcRgamma(-/-) mice subjected to occlusion and reperfusion of the coronary artery than in control FcR gamma(+/+) mice. Twenty-four hours after the reperfusion, electron microscopy of the injured tissue showed substantially more platelet aggregation and occlusive platelet microthrombi in the capillaries of the damaged areas of the wild type mice than in those of the FcR gamma(-/-) mice. Platelet Syk was scarcely activated in the FcR gamma(-/-) mice after myocardial ischemia and reperfusion, but significantly activated in the FcR gamma(+/+) mice. CD11b expression on neutrophils was elevated after myocardial ischemia and reperfusion in both mouse groups, whereas myeloperoxidase activity in the injured areas was significantly lower in the FcRgamma(-/-) mice than in the FcRgamma(+/+) mice. These results suggest that the collagen-induced activation of platelets through the FcR gamma plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcRgamma and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury.
Takaya
Norihide
N
Department of Cardiology, Juntendo University School of Medicine, 2-1-1 Hongo, Tokyo 113-8421, Japan.
Katoh
Youichi
Y
Iwabuchi
Kazuhisa
K
Hayashi
Ichiro
I
Konishi
Hakuoh
H
Itoh
Seigo
S
Okumura
Ko
K
Ra
Chisei
C
Nagaoka
Isao
I
Daida
Hiroyuki
H
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism*; D004789:Enzyme Activation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010974:Platelet Aggregation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D000072377:Syk Kinase
D018955:CD36 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse