Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon.

Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon.
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DOI:
10.4049/jimmunol.137.6.1893
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发表时间:
1986-09
影响因子:
4.4
通讯作者:
J. Pober;M. Gimbrone;L. Lapierre;D. Mendrick;W. Fiers;R. Rothlein;T. Springer
J. Pober;M. Gimbrone;L. Lapierre;D. Mendrick;W. Fiers;R. Rothlein;T. Springer
中科院分区:
医学2区
文献类型:
--
作者:
J. Pober;M. Gimbrone;L. Lapierre;D. Mendrick;W. Fiers;R. Rothlein;T. Springer

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我们利用鼠单克隆抗体与培养的人脐静脉内皮细胞(HUVE)表面的定量结合,研究了HUVE细胞对三种不同免疫介质的反应:白细胞介素1(IL - 1)、肿瘤坏死因子(TNF)和免疫干扰素(IFN - γ)。抗体H4/18可与一种内皮细胞特异性激活抗原发生反应,它不与未受刺激的HUVE细胞结合,但对受IL - 1或TNF刺激的细胞会迅速且短暂地出现诱导性结合(在4到6小时达到峰值),即使介质持续存在,到24小时也会下降到基础水平。H4/18的结合不受IFN - γ的影响。抗体RR1/1可与细胞间黏附分子1发生反应,它与未受刺激的HUVE细胞结合,但在受到IL - 1或TNF刺激后结合迅速增加(在24小时达到平台期),受到IFN - γ刺激后则缓慢增加(持续数天)。与H4/18的结合情况不同,RR1/1结合的增加在介质持续存在的情况下会持续。抗体W6/32可与HLA - A、B抗原发生反应,它与未受刺激的HUVE细胞结合,并且在受到IFN - γ或TNF处理后结合会逐渐增加(持续数天)。这些观察结果表明,HUVE细胞在对三种不同的淋巴因子作出反应时,呈现出不同但有重叠的抗原调节模式,并提示在原位观察到的内皮细胞的“激活”可能代表了几种淋巴因子介导的信号的复杂整合。
We have used the quantitative binding of murine monoclonal antibodies to the surface of cultured human umbilical vein endothelial (HUVE) cells to study the responses of HUVE cells to three different immune mediators: interleukin 1 (IL 1), tumor necrosis factor (TNF), and immune interferon (IFN-gamma). Antibody H4/18, reactive with an endothelial cell-specific activation antigen, does not bind to unstimulated HUVE cells but shows rapidly and transiently inducible binding (peak 4 to 6 hr) to cells stimulated by IL 1 or TNF that declines to basal levels by 24 hr, even in the continued presence of mediator. Binding of H4/18 is unaffected by IFN-gamma. Antibody RR1/1, reactive with intercellular adhesion molecule 1, binds to unstimulated HUVE cells, but binding is rapidly increased (plateau 24 hr) after stimulation by IL 1 or TNF and slowly increased (over several days) by IFN-gamma. In contrast to H4/18 binding, the increase in RR1/1 binding is sustained in the continued presence of mediator. Antibody W6/32, reactive with HLA-A,B antigens, binds to unstimulated HUVE cells and shows gradually progressive increases (over several days) in binding upon treatment with IFN-gamma or TNF. These observations demonstrate that HUVE cells show distinct but overlapping patterns of antigenic modulation in response to three different lymphokines, and suggest that the "activation" of endothelial cells observed in situ may represent a complex integration of several lymphokine-mediated signals.