PMID- 29112834 OWN - NLM STAT- MEDLINE DCOM- 20180124 LR - 20181010 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 93 DP - 2018 Jan TI - Natural killer cells play an essential role in resolution of antigen-induced inflammation in mice. PG - 1-8 LID - S0161-5890(17)30548-5 [pii] LID - 10.1016/j.molimm.2017.10.019 [doi] AB - This study examined whether NK cells are important for resolution of antigen-induced inflammation. C57BL/6 mice were immunized twice with methylated BSA (mBSA) and inflammation induced by intraperitoneal injection of mBSA. Mice were injected intravenously with anti-asialo GM1 (alphaASGM1) or a control antibody 24h prior to peritonitis induction and peritoneal exudate collected at different time points. Expression of surface molecules and apoptosis on peritoneal cells was determined by flow cytometry and concentration of chemokines, cytokines, soluble cytokine receptors and lipid mediators by ELISA and LC-MS/MS. Apoptosis in parathymic lymph nodes and spleens was determined by TUNEL staining. Mice administered alphaASGM1 had lower peritoneal NK cell numbers and a higher number of peritoneal neutrophils 12h after induction of inflammation than control mice. The number of neutrophils was still high in the alphaASGM1 treated mice when their number had returned to baseline levels in the control mice, 48h after induction of inflammation. Peritoneal concentrations of the neutrophil regulators G-CSF and IL-12p40 were higher at 12h in the alphaASGM1 treated mice than in the control mice, whereas concentrations of lipid mediators implicated in resolution of inflammation, i.e. LXA(4) and PGE(2), were lower. Reduced apoptosis was detected in peritoneal neutrophils as well as in draining lymph nodes and spleens from the alphaASGM1 treated mice compared with that in the control mice. In addition, alphaASGM1 treated mice had lower number of peritoneal NK cells expressing NKp46 and NKG2D, receptors implicated in NK cell-induced neutrophil apoptosis. Furthermore, alphaASGM1 treatment completely blocked the increase in CD27(+) NK cells that occurred in control mice following induction of inflammation, but CD27(+) NK cells have been suggested to have a regulatory role. These results indicate a crucial role for NK cells in resolution of antigen-induced inflammation and suggest their importance in tempering neutrophil recruitment and maintaining neutrophil apoptosis. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Anuforo, Osk U U AU - Anuforo OUU AD - Biochemistry and Molecular Biology, Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland; Department of Immunology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland; Centre for Rheumatology Research, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. FAU - Bjarnarson, Stefania P AU - Bjarnarson SP AD - Department of Immunology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland; Department of Immunology, Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland. FAU - Jonasdottir, Hulda S AU - Jonasdottir HS AD - Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands. FAU - Giera, Martin AU - Giera M AD - Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands. FAU - Hardardottir, Ingibjorg AU - Hardardottir I AD - Biochemistry and Molecular Biology, Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland. FAU - Freysdottir, Jona AU - Freysdottir J AD - Department of Immunology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland; Centre for Rheumatology Research, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland; Department of Immunology, Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland. Electronic address: jonaf@landspitali.is. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171104 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Antibodies) RN - 0 (Antigens) RN - 0 (Chemokines) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Lipoxins) RN - 0 (Receptors, Natural Killer Cell) RN - 0 (lipoxin A4) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 27432CM55Q (Serum Albumin, Bovine) RN - 37758-47-7 (G(M1) Ganglioside) RN - 71012-19-6 (asialo GM1 ganglioside) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Antibodies/immunology/therapeutic use MH - Antigens/*toxicity MH - Apoptosis/drug effects MH - Chemokines/analysis MH - Dinoprostone/analysis MH - Female MH - G(M1) Ganglioside/antagonists & inhibitors/immunology MH - Granulocyte Colony-Stimulating Factor/analysis MH - Immunophenotyping MH - Inflammation Mediators/analysis MH - Interleukin-12 Subunit p40/analysis MH - Killer Cells, Natural/drug effects/*immunology MH - Lipoxins/analysis MH - Lymph Nodes/pathology MH - Mice MH - Mice, Inbred C57BL MH - Neutrophil Infiltration/drug effects MH - Peritonitis/chemically induced/*immunology/metabolism/therapy MH - Receptors, Natural Killer Cell/analysis MH - Serum Albumin, Bovine/toxicity MH - Spleen/pathology OTO - NOTNLM OT - Apoptosis OT - NK cells OT - Neutrophils OT - Peritonitis OT - Resolution of inflammation EDAT- 2017/11/08 06:00 MHDA- 2018/01/25 06:00 CRDT- 2017/11/08 06:00 PHST- 2017/08/28 00:00 [received] PHST- 2017/10/19 00:00 [revised] PHST- 2017/10/25 00:00 [accepted] PHST- 2017/11/08 06:00 [pubmed] PHST- 2018/01/25 06:00 [medline] PHST- 2017/11/08 06:00 [entrez] AID - S0161-5890(17)30548-5 [pii] AID - 10.1016/j.molimm.2017.10.019 [doi] PST - ppublish SO - Mol Immunol. 2018 Jan;93:1-8. doi: 10.1016/j.molimm.2017.10.019. Epub 2017 Nov 4.