Abstract
Neutrophil recruitment and their mediated inflammatory responses are critical for cardiovascular 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 mouse knockouts (KO) of beta2 integrin (CD18) or blocking beta2 integrin with antibodies in multiple animals significantly reduced infarct size after myocardial I/R injury. However, the neutrophil-specific contribution of beta2 integrin to I/R injury is unknown. This study used the newly established CD18 flox/flox (hITGB2 KI) mouse strain to address this knowledge gap. We crossed them to MRP8-cre (S100A8) and confirmed the neutrophil-specific KO of beta2 integrins. Interestingly, all leukocyte subtypes were elevated in the blood of MRP8-cre CD18 flox/flox mice, indicating potential chronic inflammation. After 35 minutes of myocardial ischemia and 24 hours of reperfusion, we found MRP8-cre CD18 flox/flox mice have significantly 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 CD18 flox/flox mice. The quantification of leukocyte recruitment in hearts after I/R injury showed that male but not female MRP8-cre CD18 flox/flox mice have less recruitment of neutrophils and Ly6C high inflammatory monocytes. These results suggested sex bias of neutrophil-specific contributions of beta2 integrins in myocardial ischemia-reperfusion injury and provided new insights into beta2 integrin targeting therapies.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
