| pubmed-article:7529746 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0678133 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0035495 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0028128 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0024432 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C1456820 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C1367477 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0591833 | lld:lifeskim |
| pubmed-article:7529746 | lifeskim:mentions | umls-concept:C0058398 | lld:lifeskim |
| pubmed-article:7529746 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:7529746 | pubmed:dateCreated | 1995-2-16 | lld:pubmed |
| pubmed-article:7529746 | pubmed:abstractText | Taxol, a microtubule stabilizer with anticancer activity, mimics the actions of lipopolysaccharide (LPS) on murine macrophages in vitro. Recently, it was shown that taxol-induced macrophage activation was inhibited by the LPS antagonist Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA). To investigate the mechanisms of taxol-induced macrophage activation, the present study focused on the interaction of LPS, RsDPLA, and taxol in the activation of and binding to macrophages. Taxol alone induced murine C3H/He macrophages to secrete tumor necrosis factor alpha (TNF) and to produce nitric oxide (NO) with kinetics similar to that of LPS. Macrophages from LPS-hyporesponsive C3H/HeJ mice, in contrast, did not yield any detectable TNF and NO production in response to LPS or taxol. RsDPLA inhibited taxol-induced TNF and NO production from C3H/He macrophages in a dose-dependent manner. The inhibition by RsDPLA was specific for LPS and taxol in that RsDPLA did not inhibit heat-killed Listeria monocytogenes- or zymosan-induced TNF production. Polymyxin B blocked the inhibitory effect of RsDPLA on taxol-induced TNF production. The inhibitory activity of RsDPLA appeared to be reversible since macrophages still responded to taxol in inducing TNF production after the RsDPLA was washed out with phosphate-buffered saline prior to the addition of taxol. Taxol-induced TNF production was not inhibited by colchicine, vinblastine, or 10-deacetylbaccatine III. A mutant cell line, J7.DEF3, defective in expression of a CD14 antigen, responded equally well to taxol by producing TNF as did the parent J774.1 cells. This suggested that the activation of macrophages by taxol does not require CD14. Taxol-induced TNF production by the mutant cells was also inhibited by RsDPLA. 125I-labeled LPS and 3H-labeled taxol was reported to bind to J774.1 cells predominantly via CD14 and microtubules, respectively. The binding of 125I-labeled LPS to J7.DEF3 cells was about 30 to 40% of that to J774.1 cells. The binding of 125I-LPS to J774.1 cells was inhibited by unlabeled LPS and RsDPLA but not by taxol. On the other hand, 3H-labeled taxol bound to both J774.1 cells and J7.DEF3 cells in similar time- and dose-dependent manners. The binding of [3H]taxol to these cells was inhibited by taxol but not by LPS or RsDPLA. Although the binding studies failed to examine cross competition for binding to macrophages, a possible explanation of these results is that LPS, RsDPLA, and taxol share the same molecule(s) on murine macrophages for their functional receptor(s), which is neither CD14 nor tubulin. | lld:pubmed |
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| pubmed-article:7529746 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:7529746 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:7529746 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:7529746 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:7529746 | pubmed:issn | 0019-9567 | lld:pubmed |
| pubmed-article:7529746 | pubmed:author | pubmed-author:NakanoMM | lld:pubmed |
| pubmed-article:7529746 | pubmed:author | pubmed-author:TakayamaKK | lld:pubmed |
| pubmed-article:7529746 | pubmed:author | pubmed-author:QureshiNN | lld:pubmed |
| pubmed-article:7529746 | pubmed:author | pubmed-author:MorrisonD CDC | lld:pubmed |
| pubmed-article:7529746 | pubmed:author | pubmed-author:KirikaeTT | lld:pubmed |
