Neutrophil-specific CD18 deletion protect male but not female mice from myocardial ischemia-reperfusion injury 2039

Abstract Description Neutrophil-mediated inflammatory responses are critical for inflammatory diseases, including myocardial ischemia-reperfusion (I/R) injury, which accounts for 9% mortality and 10% morbidity rates in ischemic heart disease patients. Blocking leukocyte recruitment in CD18 knockout (KO) mice significantly reduced infarct size after myocardial I/R injury. However, the neutrophil-specific contribution of CD18 to I/R injury is unknown. This study used the newly established CD18flox/flox mouse strain to address this knowledge gap. We crossed them to MRP8-cre mice and confirmed the neutrophil-specific CD18 deletion. Interestingly, all leukocyte subtypes were elevated in the blood of MRP8-cre CD18flox/flox mice, indicating potential chronic inflammation. After myocardial I/R, we found that MRP8-cre CD18flox/flox mice had reduced infarct size compared to cre- controls. However, if we distinguish the sex in analysis, we only saw a significant alleviation in male but not female MRP8-cre CD18flox/flox mice. The quantification of leukocyte recruitment in hearts after I/R injury showed that male but not female MRP8-cre CD18flox/flox mice have less recruitment of neutrophils and Ly6Chigh inflammatory monocytes. These results suggested sex bias of neutrophil-specific contributions of CD18 integrins in myocardial I/R injury and provided new insights into integrin targeting therapies. Funding Sources This research was supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute, USA (R01HL145454, R41HL156322, and R44HL152710) and a startup fund from UConn Health. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)