Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice.
Previous studies have demonstrated that circulating neutrophils (PMNs) contribute to the pathophysiology of myocardial ischemia-reperfusion (MI/R) injury. PMN-endothelial cell interactions are highly regulated by adhesive interactions between PMN CD11/CD18 and coronary endothelial cell intercellular adhesion molecule-1 (ICAM-1). We investigated the effects of MI/R in wild-type, CD18-, and ICAM-1-deficient (-/-) mice. Wild-type (n = 6), CD18 -/- (n = 6), and ICAM-1 -/- (n = 6) mice were subjected to 30 min of myocardial ischemia and 120 min of reperfusion to determine the extent of PMN infiltration and myocardial cell necrosis. Myocardial infarction (% of the area at risk) was 45.1 +/- 5.9 in wild-type mouse hearts. In contrast, the extent of myocardial infarction was significantly (P < 0.05) reduced in the CD18 (19.3 +/- 5.1%)- and ICAM-1 (17.9 +/- 3.2%)-deficient mice. Similarly, PMN infiltration into the ischemic-reperfused myocardium was attenuated by 54% in the CD18 -/- mice and by 32% in ICAM-1 -/- mice compared with wild-type hearts. Deficiency in either CD18 or ICAM-1 expression results in a marked reduction in PMN accumulation and myocardial necrosis after acute MI/R.
Palazzo
A J
AJ
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3392, USA.
Jones
S P
SP
Girod
W G
WG
Anderson
D C
DC
Granger
D N
DN
Lefer
D J
DJ
D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000502:physiology*; D002908:Chronic Disease; D006439:Hemodynamics / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000097:blood / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D012016:Reference Values
D018821:CD18 Antigens; D018799:Intercellular Adhesion Molecule-1