title: Mast cell deficiency in Kit(W-sh) mice does not impair antibody-mediated arthritis.
abstract: We previously reported that joint swelling, synovial thickening, and cartilage matrix depletion induced by the injection of anti-collagen monoclonal antibodies and lipopolysaccharide (LPS) in BALB/c mice are increased in the absence of inhibitory leukocyte immunoglobulin (Ig)-like receptor B4 (LILRB4; formerly gp49B1) in a neutrophil-dependent manner. Because both mast cells and neutrophils express LILRB4, we sought a mast cell requirement with mast cell-deficient mouse strains, but unexpectedly obtained full arthritis in Kit(W-sh) mice and full resistance in Kit(W/KitW-v) mice. Kit(W-sh) mice were indeed mast cell deficient as assessed by histology and the absence of IgE/mast cell-dependent passive cutaneous anaphylaxis in the ear and joint as well as passive systemic anaphylaxis. Deletion of LILRB4 in Kit(W-sh) mice exacerbated anti-collagen/LPS-induced joint swelling that was abolished by neutrophil depletion, establishing a counterregulatory role for LILRB4 in the absence of mast cells. Whereas blood neutrophil levels and LPS-elicited tissue neutrophilia were equal in Kit(W-sh) and Kit+ mice, both were impaired in Kit(W/KitW-v) mice. Although both strains are mast cell deficient and protected from IgE-mediated anaphylactic reactions, their dramatically different responses to autoantibody-mediated, neutrophil-dependent immune complex arthritis suggest that other host differences determine the extent of mast cell involvement. Thus, a conclusion for an absolute mast cell role in a pathobiologic process requires evidence from both strains.
authors.affiliation: Department of Medicine, Harvard Medical School, and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Friend
authors.forename: K Frank
authors.initials: KF
authors.lastname: Austen
authors.forename: Howard R
authors.initials: HR
authors.lastname: Katz
mesh_terms: D000818:Animals; D000906:Antibodies; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology*; D003094:Collagen / Q000276:immunology; D007592:Joint Diseases / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000276:immunology
chemical_list: D000906:Antibodies; C489448:Lilrb4 protein, mouse; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D003094:Collagen; D019009:Proto-Oncogene Proteins c-kit