The mast cell tumor necrosis factor α response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48

被引:200
作者
Malaviya, R
Gao, ZM
Thankavel, K
van der Merwe, PA
Abraham, SN
机构
[1] Duke Univ, Med Ctr, Dept Pathol & Microbiol, Durham, NC 27710 USA
[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
关键词
D O I
10.1073/pnas.96.14.8110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页码:8110 / 8115
页数:6
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