Sex-specific and immune-cell-specific contributions of CD18 in myocardial ischemia-reperfusion injury

Abstract Leukocyte recruitment and their mediated inflammatory responses are critical for cardiovascular diseases, including myocardial ischemia-reperfusion (I/R) injury. Blocking leukocyte in mouse knockouts (KO) of beta2 integrin (CD18) or blocking CD18 with antibodies multiple animals significantly reduced infarct size after I/R However, the cell-specific contribution to injury is unknown. In this study, we used newly established flox/flox(hITGB2 KI) mice address knowledge gap. We crossed them CSF1R-cre (CD115) MRP8-cre (S100A8) tested KO different leukocytes. Interestingly, flox/floxunexpectedly deleted all peripheral blood leukocytes, neutrophils, monocytes, CD4 T cells, CD8 B NK cells. It also elevated cell number these leukocytes blood. flox/floxmice, was only knocked out neutrophils but not other And neutrophil After 35 minutes ischemia 24 hours reperfusion, found both flox/floxand flox/floxmice have compared cre-controls. if distinguish sex analysis, a significant alleviation female male flox/floxmice. contrast, observed These results suggested sex-specific immune-cell-specific contributions provided new insights into targeting therapies. This research supported by grants from National Institutes Health, Heart, Lung, Blood Institute, USA (R01HL145454, R41HL156322, R44HL152710) startup fund UConn Health.