Mast cell deficiency in Kit(W-sh) mice does not impair antibody-mediated arthritis.

Mast cell deficiency in Kit(W-sh) mice does not impair antibody-mediated arthritis.
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DOI:
10.1084/jem.20071391
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发表时间:
2007-11-26
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Katz HR
Katz HR
中科院分区:
其他
文献类型:
--
作者:
Zhou JS;Xing W;Friend DS;Austen KF;Katz HR

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我们之前报道过,在缺乏抑制性白细胞免疫球蛋白(Ig)样受体B4 (LILRB4,以前称为gp49B1)的情况下,注射抗胶原单克隆抗体和脂多糖(LPS)诱导的BALB/c小鼠关节肿胀、滑膜增厚和软骨基质耗散以中性粒细胞依赖的方式增加。由于肥大细胞和中性粒细胞都表达LILRB4,我们在肥大细胞缺陷小鼠株中寻找肥大细胞需求,但意外地在KitW-sh小鼠中获得完全关节炎,在KitW/KitW-v小鼠中获得完全耐药。通过组织学评估,KitW-sh小鼠确实存在肥大细胞缺陷,耳朵和关节中没有IgE/肥大细胞依赖性被动皮肤过敏反应,以及被动全身过敏反应。在KitW-sh小鼠中,LILRB4的缺失加重了抗胶原/脂多糖诱导的关节肿胀,这种肿胀被中性粒细胞消耗所消除,在肥大细胞缺失的情况下,LILRB4发挥了反调节作用。KitW-sh和Kit+小鼠的血液中性粒细胞水平和lps诱导的组织中性粒细胞水平相等,而KitW/KitW-v小鼠的两者均受损。尽管这两种毒株均存在肥大细胞缺陷,且不受ige介导的过敏反应的影响,但它们对自身抗体介导的中性粒细胞依赖性免疫复合物关节炎的显著不同反应表明,其他宿主差异决定了肥大细胞的参与程度。因此,关于肥大细胞在病理过程中的绝对作用的结论需要来自两个菌株的证据。
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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