Richter J, Zetterberg E
Department of Medicine, University Hospital, Lund, Sweden.
J Leukoc Biol. 1994 Oct;56(4):525-7. doi: 10.1002/jlb.56.4.525.
Tumor necrosis factor (TNF) is a potent activator of neutrophil granulocytes, which acts via two cell-surface receptors: the p55-TNF receptor (TNF-R55) and the p75-TNF receptor (TNF-R75). Proteolytic cleavage of the extracellular region of the receptors results in formation of soluble TNF-binding proteins, TNF-R55-BP and TNF-R75-BP. We recently reported that adherence alone, without any further stimuli, causes release of both TNF-R55-BP and TNF-R75-BP and that both leukocyte-integrin-dependent and non-integrin-dependent adherence mechanisms can modulate TNF receptor expression. In the present work we show that crosslinking of a mAb to the adhesion protein L-selectin (TQ1) on the surface of neutrophils results in downregulation of TNF-receptor binding capacity. Furthermore, when the fluctuations of cytosolic free calcium found in adherent neutrophils were blocked with the cell-permeable calcium chelator BAPTA, adherence-induced release of TNF-R55-BP was inhibited. We have shown that adherence, via mechanisms involving two adhesion proteins, L-selectin and the CD11/CD18 leukocyte integrins, and fluctuations of cytosolic free calcium, can result in downregulation of neutrophil TNF-receptors.
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-TNF受体（TNF-R55）和p75-TNF受体（TNF-R75）。受体细胞外区域的蛋白水解切割导致可溶性TNF结合蛋白、TNF-R55-BP和TNF-R75-BP的形成。我们最近报道，仅粘附，无需任何进一步刺激，就会导致TNF-R55-BP和TNF-R75-BP的释放，并且白细胞整合素依赖性和非整合素依赖性粘附机制均可调节TNF受体表达。在本研究中，我们表明，单克隆抗体与中性粒细胞表面粘附蛋白L-选择素（TQ1）交联会导致TNF受体结合能力下调。此外，当用可透过细胞的钙螯合剂BAPTA阻断粘附中性粒细胞中发现的胞质游离钙波动时，粘附诱导的TNF-R55-BP释放受到抑制。我们已经表明，通过涉及两种粘附蛋白L-选择素和CD11/CD18白细胞整合素的机制以及胞质游离钙的波动，粘附可导致中性粒细胞TNF受体下调。
