C5aR-mediated myocardial ischemia/reperfusion injury.
The complement system activation can mediate myocardial ischemia and reperfusion (I/R). Inhibition of C5a activity reveals attenuation of I/R-induced myocardial infarct size. However, the contribution of C5a receptor (C5aR) to I/R injury remains to be unknown. Here, we reported that both mRNA and protein for the C5aR were constitutively expressed on cardiomyocytes and upregulated as a function of time after I/R-induced myocardial cell injury in mice. Blockade of C5aR markedly decreased microvascular permeability in ischemic myocardial area and leukocyte adherence to coronary artery endothelium. Importantly, the blocking of C5aR with an anti-C5aR antibody was associated with inhibition in activation of protein kinase C delta (PKC-delta) and induction of PKC-mediated mitogen-activated protein kinase phosphatases-1 (MKP-1) leading to the increased activity of p42/p44 mitogen-activated protein (MAP) kinase cascade. These data provide evidence that C5aR-mediated myocardial cell injury is an important pathogenic factor, and that C5aR blockade may be useful therapeutic targets for the prevention of myocardial I/R injury.
Zhang
Haimou
H
Center for Infection and Immunity Research, School of Life Sciences, Hubei University, 11 XueYuan Road, Wuhan, Hubei, PR China.
Qin
Gangjian
G
Liang
Gang
G
Li
Jinan
J
Barrington
Robert A
RA
Liu
Dong-Xu
DX
D000818:Animals; D002199:Capillary Permeability / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000276:immunology*; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000276:immunology*; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology*
C488033:C5AR1 protein, human; D018836:Inflammation Mediators; D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement