The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23.

The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23.
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DOI:
10.1083/jcb.144.4.767
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发表时间:
1999-02-22
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Sarfati M
Sarfati M
中科院分区:
其他
文献类型:
--
作者:
Hermann P;Armant M;Brown E;Rubio M;Ishihara H;Ulrich D;Caspary RG;Lindberg FP;Armitage R;Maliszewski C;Delespesse G;Sarfati M

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Vitronectin受体α-v-β-3整合素在肿瘤细胞侵袭、血管生成和吞噬凋亡细胞中起重要作用。CD47是多跨跨膜受体家族的一员,在生理和功能上都与玻璃连结蛋白受体(VNR)相关。虽然VN不是β的配体,但抗CD47和CD3单抗抑制VN,但不能抑制纤维连接蛋白(FN)的结合和功能。在这里,我们发现抗CD47、抗β3单抗和VN,而不是FN,可以抑制sCD23介导的促炎功能(肿瘤坏死因子α、IL-12和干扰素-γ的释放)。令人惊讶的是,抗CD47和β3单抗不能阻止α与β3+T细胞的结合,而VN和αv单抗(克隆AMF7)确实抑制了sCD23的结合,提示vN复合体可能是sCD23的功能性受体。CD2 3可直接与αv+β3+/CD4 7−细胞结合,但共表达CD4 7可增加结合力。此外,sCD23还能与纯化的αv蛋白和单个人αv链CHO转染体结合。我们认为,VNR及其相关的CD47分子可能是一种新的sCD23受体,介导其促炎活性,并可能参与免疫应答的炎症过程。
The vitronectin receptor, αvβ3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and β3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-β3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-α, IL-12, and IFN-γ release). Surprisingly, anti-CD47 and β3 mAbs do not block sCD23 binding to αv +β3 + T cell lines, whereas Vn and an αv mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds αv +β3 +/CD47− cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified αv protein and a single human αv chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.
DOI: 10.1073/pnas.92.9.3978
发表时间: 1995-04-25
影响因子: 11.1
作者:
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发表时间: 1996-10
期刊: The Journal of cell biology
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发表时间: 1996-09-01
影响因子: 7.8
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发表时间: 1993-01-01
影响因子: 2.8
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发表时间: 1995-07-01
期刊: IMMUNITY
影响因子: 32.4
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