The mast cell tumor necrosis factor α response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48
The mast cell tumor necrosis factor α response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48
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DOI：
10.1073/pnas.96.14.8110
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Abraham, SN
中科院分区：
文献类型：
--
作者：
Malaviya, R;Gao, ZM;Abraham, SN
肥大细胞在IgE介导的超敏反应中的有害作用是众所周知的，但其生理作用仍然是一个谜。最近的几项研究报道，肥大细胞通过释放肿瘤坏死因子α（TNF-α）将中性粒细胞募集到肠细菌感染部位，在小鼠先天免疫中发挥关键作用。在某些情况下，当这些细胞直接结合大肠杆菌表面上的FimH时，肥大细胞TNF-α反应被触发。我们已经鉴定了CD 48，一种糖基磷脂酰肌醇锚定分子，是啮齿动物肥大细胞膜组分中的互补FimH结合部分。我们发现（i）用抗CD 48或磷脂酶C的抗体预处理肥大细胞膜可抑制FimH（+）E的结合。coli，（ii）FimH（+）E.（iii）当用CD 48 cDNA转染中国仓鼠卵巢（CHO）细胞时，FimH（+）细菌与这些细胞的结合显著增加;（iv）CD 48抗体特异性阻断肥大细胞对FimH（+）E.杆菌因此，CD 48是肥大细胞上功能相关的微生物受体，在触发炎症中起作用。
Mast cells are well known for their harmful role in IgE-mediated hypersensitivity reactions, but their physiological role remains a mystery. Several recent studies have reported that mast cells play a critical role in innate immunity in mice by releasing tumor necrosis factor alpha (TNF-alpha) to recruit,neutrophils to sites of enterobacterial infection. In some cases, the mast cell TNF-alpha response was triggered when these cells directly bound FimH on the surface of Escherichia coli, We have identified CD48, a glycosylphosphatidylinositol-anchored molecule, to be the complementary FimH-binding moiety in rodent mast cell membrane fractions. We showed that (i) pretreatment of mast cell membranes with antibodies to CD48 or phospholipase C inhibited binding of FimH(+) E. coli, (ii) FimH(+) E. coli but not a FimH(-) derivative bound isolated CD48 in a mannose-inhibitable manner, (iii) binding of FimH(+) bacteria to Chinese hamster ovary (CHO) cells was markedly increased when these cells were transfected with CD48 cDNA, and (iv) antibodies to CD48 specifically blocked the mast cell TNF-alpha response to FimH(+) E. coli. Thus, CD48 is a functionally relevant microbial receptor on mast cells that plays a role in triggering inflammation.