Lipocalin-2 promotes m1 macrophages polarization in a mouse cardiac ischaemia-reperfusion injury model.

Abstract

Ischaemia-reperfusion (IR) injury is a major issue in cardiac transplantation. Inflammatory processes play a major role in myocardial IR injury. Lipocalin-2 (Lcn2), which is also known as neutrophil gelatinase-associated lipocalin, has multiple functions that include the regulation of cell death/survival, cell migration/invasion, cell differentiation and iron delivery. In our study, the hearts of C57BL/6 mice were flushed with and stored in cold Bretschneider solution for 8h and then transplanted into a syngeneic recipient. We found that Lcn2 neutralization decreased the recruitment of neutrophils and macrophages. Troponin T (TnT) production, 24h after myocardial IR injury, was reduced through anti-Lcn2 antibody administration. The cardiac output at 60mmHg of afterload pressure was significantly increased in hearts administrated with anti-Lcn2 antibody administration (anti-Lcn-2: 58.9±5.62ml/min; control: 25.8±4.1ml/min; P<0.05). Anti-Lcn2 antibody treatment suppressed M1 marker (IL-12, IL-23 and iNOS) expression but increased M2 marker (IL-10, Arg1 and Mrc1) expression. Furthermore, in our vitro and vivo experiments, we found that anti-Lcn2 antibody treatment failed to induce M1-related gene expression in response to LPS and that Lcn2 neutralization enhanced the expression of M2-related genes following IL-4 treatment. In conclusion, Lcn2 promotes M1 polarization, and Lcn2 neutralization attenuates cardiac IR injury.