| pubmed-article:7691950 | pubmed:abstractText | Two cell types, monocytes/macrophages and neutrophilic granulocytes, play a prominent role in the pathogenic effects of endotoxins during Gram-negative infections. We previously established that nanomolar concentrations of LPS induce the expression of new specific LPS-binding sites (LpsR) in bone marrow granulocytes of LPS-responsive mice. To examine this induction process further, we asked whether it, like other LPS activities, can be mediated by TNF-alpha. We report that exogenous rTNF-alpha can induce LpsR expression in bone marrow cells (BMC) from both LPS-responsive (C3H/HeOU) and LPS-hyporesponsive (C3H/HeJ) mice. In BMC, LPS elicited a down-regulation of the TNF-alpha receptors (TNF-R) without direct binding to TNF-R. On the other hand, taxol, a microtubule stabilizer that has shown LPS mimetic activity in macrophages, was unable to elicit LpsR expression or induce TNF-R down-regulation in BMC. Thus, unlike the LPS-signaling receptor of macrophages, that of BMC is apparently not functionally associated with microtubules. The LPS-induced expression of LpsR was inhibited only partially with an anti-TNF-alpha serum, and with dexamethasone, suggesting that an autocrine activity of endogenous TNF-alpha cannot alone account for the LPS effect. Comparative analyses also indicated that dexamethasone inhibited the LPS-induced increase of LpsR, but enhanced the number of TNF-induced LpsR+ BMC. Furthermore, the synthetic lipid PPDm2 (a 1,4-bisphosphorylated and N,N-diacylated derivative of 2,3-diamino-2,3-dideoxy-D-glucose) inhibited LPS-induced, but not TNF-induced, expression of LpsR. These data show that in BMC, LPS and TNF-alpha induce LpsR expression by different mechanisms. | lld:pubmed |
