Mast cell deficiency in KitW-sh mice does not impair antibody-mediated arthritis

JS Zhou, W Xing, DS Friend, KF Austen… - The Journal of …, 2007 - rupress.org
JS Zhou, W Xing, DS Friend, KF Austen, HR Katz
The Journal of experimental medicine, 2007rupress.org
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 KitW-sh mice …
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 KitW-sh mice and full resistance in KitW/KitW-v mice. KitW-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 KitW-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 KitW-sh and Kit+ mice, both were impaired in KitW/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.
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