title: 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 8 h and then transplanted into a syngeneic recipient. We found that Lcn2 neutralization decreased the recruitment of neutrophils and macrophages. Troponin T (TnT) production, 24 h after myocardial IR injury, was reduced through anti-Lcn2 antibody administration. The cardiac output at 60 mmHg of afterload pressure was significantly increased in hearts administrated with anti-Lcn2 antibody administration (anti-Lcn-2: 58.9 ± 5.62 ml/min; control: 25.8 ± 4.1 ml/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.
authors.affiliation: Department of Gynaecology and Obstetrics, Xiangyan Central Hospital, Hubei University of Arts and Science, Xiangyang, China.
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: H
authors.initials: H
authors.lastname: Xing
authors.forename: X
authors.initials: X
authors.lastname: Mao
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Li
mesh_terms: D000209:Acute-Phase Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001119:Arginase / Q000096:biosynthesis; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016027:Heart Transplantation; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology* / Q000637:transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000473:pathology*; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D011971:Receptors, Immunologic; D015427:Reperfusion Injury / Q000473:pathology*; D014336:Troponin / Q000096:biosynthesis
chemical_list: D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; C556062:IL10 protein, mouse; D053759:Interleukin-23; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D015513:Oncogene Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014336:Troponin; C071332:Lcn2 protein, mouse; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase