title: CD97 antibody depletes granulocytes in mice under conditions of acute inflammation via a Fc receptor-dependent mechanism.
abstract: Antibodies to the pan-leukocyte adhesion-GPCR CD97 efficiently block neutrophil recruitment in mice, thereby reducing antibacterial host defense, inflammatory disease, and hematopoietic stem cell mobilization. Here, we investigated the working mechanism of the CD97 antibody 1B2. Applying sterile models of inflammation, intravital microscopy, and mice deficient for the CD97L CD55, the complement component C3, or the FcR common γ-chain, we show that 1B2 acts in vivo independent of ligand-binding interference by depleting PMN granulocytes in bone marrow and blood. Granulocyte depletion with 1B2 involved FcR but not complement activation and was associated with increased serum levels of TNF and other proinflammatory cytokines. Notably, depletion of granulocytes by CD97 antibody required acute inflammation, suggesting a mechanism of conditional, antibody-mediated granulocytopenia.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Henrike
authors.initials: H
authors.lastname: Veninga
authors.forename: Dorien M
authors.initials: DM
authors.lastname: de Groot
authors.forename: Natalie
authors.initials: N
authors.lastname: McCloskey
authors.forename: Bronwyn M
authors.initials: BM
authors.lastname: Owens
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dessing
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
authors.forename: Hans
authors.initials: H
authors.lastname: van Eenennaam
authors.forename: Annemieke M
authors.initials: AM
authors.lastname: Boots
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000918:Antibody Specificity / Q000187:drug effects; D018958:CD55 Antigens / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007975:Leukotriene B4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009503:Neutropenia / Q000150:complications / Q000276:immunology / Q000473:pathology; D010538:Peritonitis / Q000150:complications / Q000276:immunology / Q000473:pathology; D011961:Receptors, Fc / Q000276:immunology*; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C490633:Adgre5 protein, mouse; D019138:Antibodies, Blocking; D018958:CD55 Antigens; D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4