Lipopolysaccharide LPS-mediated soluble TNF receptor release and TNF receptor expression by monocytes. Role of CD14, LPS binding protein, and bactericidal/permeability-increasing protein.
Lipopolysaccharide LPS-mediated soluble TNF receptor release and TNF receptor expression by monocytes. Role of CD14, LPS binding protein, and bactericidal/permeability-increasing protein.
复制标题
脂多糖 LPS 介导的可溶性 TNF 受体释放和单核细胞的 TNF 受体表达。
作者：
J. Leeuwenberg;M. Dentener;W. Buurman
以前，我们证明了两种可溶性肿瘤坏死因子受体，TNF-R55以及sTNF-R75，在体外由单核细胞组成性释放，并且这种释放在激活后显著增强。由于LPS是单核细胞的重要激活剂，我们研究了LPS对单核细胞释放sTNF-R的影响。发现sTNF-R75的释放，而不是sTNF-R55的释放（或最低限度地），在用LPS活化后增强，在大约2天后达到平台水平。CD14是LPS的膜受体之一，是该过程中的中间体，如使用针对CD14的mAb的实验所示。在无血清条件下，LPS诱导的sTNF-R75释放比有血清存在下的释放少，表明血清蛋白参与。LPS结合蛋白（LBP）的加入在无血清条件下增强了LPS诱导的sTNF-R75的释放，但在有血清的情况下没有影响。另一方面，已知具有LPS中和活性的杀菌/通透性增加蛋白（BPI）抑制LPS诱导的sTNF-R75释放。此外，两种类型的TNF-R的细胞表面表达被示出由LPS、LBP和BPI控制。LPS在1 h内引起TNF-R55和TNF-R75表达的完全降低，随后在24 h后两种受体的重新表达增强。LBP可增加表达的下调，而BPI可抵消LPS诱导的下调。能够灭活TNF的sTNF-R75的LPS增强的释放，以及LPS诱导的TNF-R表达的初始下调，导致假定的对TNF的暂时无反应性，这可能与仔细控制TNF作用的生理机制相同。
Previously we demonstrated that two soluble(s) tumor necrosis factor receptors, TNF-R55 as well as sTNF-R75, are constitutively released in vitro by monocytes, and that this release was markedly enhanced after activation. Because LPS is an important activator of monocytes, we investigated the effect of LPS on sTNF-R release by monocytes. It was found that release of sTNF-R75, but not (or minimally) release of sTNF-R55, was enhanced after activation with LPS, reaching plateau levels after approximately 2 days. CD14, one of the membrane receptors for LPS, is an intermediate in this process, as shown in experiments using mAb directed against CD14. Under serum-free conditions, LPS-induced sTNF-R75 release was less as compared with release in the presence of serum, suggesting involvement of serum proteins. Addition of LPS binding protein (LBP) enhanced the LPS-induced sTNF-R75 release under serum-free conditions, but had no effect in the presence of serum. On the other hand, bactericidal/permeability-increasing protein (BPI), known to possess LPS neutralizing activity, inhibited LPS-induced sTNF-R75 release. Furthermore, cell surface expression of both types of TNF-R was shown to be controlled by LPS, LBP, and BPI. LPS caused, within 1 h, a complete reduction of TNF-R55 as well as TNF-R75 expression, followed by enhanced re-expression of both receptors after 24 h. The down-modulation of expression was increased by LBP, whereas BPI counteracted the LPS-induced down-regulation. The LPS-enhanced release of sTNF-R75, capable of inactivation of TNF, as well as LPS-induced initial down-modulation of TNF-R expression leading to postulated temporary unresponsiveness to TNF may share in a physiological mechanism to carefully control the effects of TNF.