PMID- 28465620 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 May 2 TI - IVIG regulates the survival of human but not mouse neutrophils. PG - 1296 LID - 10.1038/s41598-017-01404-0 [doi] LID - 1296 AB - Intravenous immunoglobulin (IVIG) are purified IgG preparations made from the pooled plasma from thousands of healthy donors and are being tested in preclinical mouse models. Inherent challenges, however, are the pluripotency of IVIG and its xenogeneicity in animals. IVIG can alter the viability of human neutrophils via agonistic antibodies to Fas and Siglec-9. In this study, we compared the effects of IVIG on human and mouse neutrophils using different death assays. Different commercial IVIG preparations similarly induced cytokine-dependent death in human neutrophils, whereas they had no effects on the survival of either peripheral blood or bone marrow neutrophils from C57BL/6 or BALB/c mice. F(ab')(2) but not Fc fragments of IVIG induced death of human neutrophils, whereas neither of these IVIG fragments, nor agonistic monoclonal antibodies to human Fas or Siglec-9 affected the viability of mouse neutrophils. Pooled mouse IgG, which exhibited a different immunoprofile compared to IVIG, also had no effect on mouse cells. Together, these observations demonstrate that effects of IVIG on neutrophil survival are not adequately reflected in current mouse models, despite the key role of these cells in human inflammatory and autoimmune diseases. FAU - Schneider, Christoph AU - Schneider C AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. FAU - Wicki, Simone AU - Wicki S AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. FAU - Graeter, Stefanie AU - Graeter S AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. FAU - Timcheva, Tankica M AU - Timcheva TM AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. FAU - Keller, Christian W AU - Keller CW AD - Institute of Experimental Immunology, Laboratory of Neuroinflammation, University of Zurich, Zurich, Switzerland. FAU - Quast, Isaak AU - Quast I AUID- ORCID: 0000-0001-6517-8537 AD - Institute of Experimental Immunology, Laboratory of Neuroinflammation, University of Zurich, Zurich, Switzerland. AD - Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Australia. FAU - Leontyev, Danila AU - Leontyev D AD - Department of Medicine, University of Toronto and Centre for Innovation, Canadian Blood Services, Toronto, Ontario, Canada. FAU - Djoumerska-Alexieva, Iglika K AU - Djoumerska-Alexieva IK AD - Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. FAU - Kasermann, Fabian AU - Kasermann F AD - CSL Behring, Research, Bern, Switzerland. FAU - Jakob, Stephan M AU - Jakob SM AD - Department of Intensive Care Medicine, University Hospital Bern (Inselspital), University of Bern, Bern, Switzerland. FAU - Dimitrova, Petya A AU - Dimitrova PA AD - Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. FAU - Branch, Donald R AU - Branch DR AD - Department of Medicine, University of Toronto and Centre for Innovation, Canadian Blood Services, Toronto, Ontario, Canada. FAU - Cummings, Richard D AU - Cummings RD AD - Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. FAU - Lunemann, Jan D AU - Lunemann JD AD - Institute of Experimental Immunology, Laboratory of Neuroinflammation, University of Zurich, Zurich, Switzerland. FAU - Kaufmann, Thomas AU - Kaufmann T AUID- ORCID: 0000-0001-9906-874X AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. FAU - Simon, Hans-Uwe AU - Simon HU AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. FAU - von Gunten, Stephan AU - von Gunten S AUID- ORCID: 0000-0002-2753-8738 AD - Institute of Pharmacology, University of Bern, Bern, Switzerland. stephan.vongunten@pki.unibe.ch. LA - eng GR - P41 GM103694/GM/NIGMS NIH HHS/United States GR - R24 GM098791/GM/NIGMS NIH HHS/United States GR - U54 GM062116/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170502 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (SIGLEC9 protein, human) RN - 0 (Sialic Acid Binding Immunoglobulin-like Lectins) RN - 0 (fas Receptor) SB - IM MH - Animals MH - Antibodies, Monoclonal/administration & dosage/immunology MH - Antigens, CD/immunology MH - Cell Survival/*drug effects/immunology MH - Humans MH - Immunoglobulin Fc Fragments/immunology MH - Immunoglobulin G/administration & dosage/*immunology MH - Immunoglobulins, Intravenous/*administration & dosage/immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Neutrophils/*drug effects/immunology MH - Sialic Acid Binding Immunoglobulin-like Lectins/immunology MH - fas Receptor/immunology PMC - PMC5430961 COIS- The authors declare that they have no competing interests. EDAT- 2017/05/04 06:00 MHDA- 2018/09/11 06:00 PMCR- 2017/05/02 CRDT- 2017/05/04 06:00 PHST- 2016/06/01 00:00 [received] PHST- 2017/03/30 00:00 [accepted] PHST- 2017/05/04 06:00 [entrez] PHST- 2017/05/04 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] PHST- 2017/05/02 00:00 [pmc-release] AID - 10.1038/s41598-017-01404-0 [pii] AID - 1404 [pii] AID - 10.1038/s41598-017-01404-0 [doi] PST - epublish SO - Sci Rep. 2017 May 2;7(1):1296. doi: 10.1038/s41598-017-01404-0.