Richter J, Gullberg U, Lantz M
Department of Medicine, University Hospital, Lund, Sweden.
J Immunol. 1995 Apr 15;154(8):4142-9.
TNF, a potent activator of neutrophil granulocytes, acts via two cell-surface receptors: the p55-TNF receptor (TNF-R55) and the p75-TNF receptor (TNF-R75), which can be cleaved from the cell surface and thus form soluble TNF-binding proteins (TNF-BP). The role of the two receptors in activation of the neutrophil respiratory burst was investigated. Two mAbs reacting with TNF-R55 (H398 and TBP2) induced O2 release in a similar manner but to a lesser extent than TNF. TBP2, however, required preincubation at 4 degrees C to exert its effect. Preincubation of neutrophils (both at 4 and 37 degrees C) with mAb to TNF-R75 decreased TNF-induced superoxide anion production by 67 and 64%, respectively, indicating the essential role also for TNF-R75 in neutrophil activation. This inhibitory effect could not be explained by cross-down-regulation of TNF-R55 because the TNF-R75 mAb had no effect on TNF binding to TNF-R55 as determined by binding of 125I-labeled TNF or release of TNF-R55-BP as measured by ELISA. Furthermore, the TNF-R75 mAb did not decrease superoxide anion generation induced by the TNF-R55 mAb H398, thus ruling out that the inhibitory effect of the TNF-R75 mAb is due to inhibition of the signaling pathway downstream of TNF-R55. In contrast to the TNF-R75 mAb, TNF-R55 mAbs induced down-regulation of TNF-R75 and shedding of both TNF-R55-BP and TNF-R75-BP. We conclude that both TNF-R55 and TNF-R75 are involved in TNF-induced activation of the neutrophil respiratory burst.
肿瘤坏死因子（TNF）是中性粒细胞的一种强效激活剂，它通过两种细胞表面受体发挥作用：p55肿瘤坏死因子受体（TNF-R55）和p75肿瘤坏死因子受体（TNF-R75），这两种受体可从细胞表面裂解，从而形成可溶性肿瘤坏死因子结合蛋白（TNF-BP）。研究了这两种受体在激活中性粒细胞呼吸爆发中的作用。两种与TNF-R55反应的单克隆抗体（H398和TBP2）以类似方式诱导氧气释放，但程度低于TNF。然而，TBP2需要在4℃预孵育才能发挥其作用。用抗TNF-R75单克隆抗体对中性粒细胞进行预孵育（4℃和37℃），分别使TNF诱导的超氧阴离子产生减少67%和64%，表明TNF-R75在中性粒细胞激活中也起着重要作用。这种抑制作用不能用TNF-R55的交叉下调来解释，因为通过125I标记的TNF结合或ELISA测定的TNF-R55-BP释放确定，TNF-R75单克隆抗体对TNF与TNF-R55的结合没有影响。此外，TNF-R75单克隆抗体不会降低由TNF-R55单克隆抗体H398诱导的超氧阴离子生成，因此排除了TNF-R75单克隆抗体的抑制作用是由于抑制TNF-R55下游信号通路的可能性。与TNF-R75单克隆抗体相反，TNF-R55单克隆抗体诱导TNF-R75下调以及TNF-R55-BP和TNF-R75-BP的脱落。我们得出结论，TNF-R55和TNF-R75都参与了TNF诱导的中性粒细胞呼吸爆发激活。
