B cell triggering properties of a nontoxic derivative of amphotericin B.
B cell triggering properties of a nontoxic derivative of amphotericin B.
复制标题
两性霉素 B 无毒衍生物的 B 细胞触发特性。
作者：
P. Sarthou;D. Primi;P. Cazenave
两性霉素B(AMB)是一种抗真菌多烯类抗生素，已有多项研究报道了其免疫调节特性。然而，关于这一主题的许多发现是相互矛盾的，AMB对免疫系统作用的确切机制尚不清楚。由于AMB的毒性和有限的溶解性可能是造成这些差异的原因，我们合成了一种无毒的AMB衍生物(AMBSH)，并研究了其对小鼠B细胞的免疫调节作用。我们的结果表明，AMBSH在AMB弱有效或毒性的条件下能诱导强烈的增殖反应，并且AMBSH支持成熟的免疫球蛋白的分泌。当次适宜剂量的内毒素(或BCGF)与AMBSH同时存在时，对B细胞的增殖有协同作用。频率分析表明，虽然只有有限数量的B细胞对AMBSH单独反应，但在这种多烯存在的情况下，大量B细胞将对亚阈值剂量的内毒素产生反应。最后，我们发现，脾细胞与AMBSH孵育后，Ia的表达增加。根据多烯类抗生素的膜解离特性对这些结果进行了讨论。
The immunomodulating properties of amphotericin B (AMB), an antifungal polyene antibiotic, have been reported in multiple studies. However, many findings on the subject are conflicting, and the precise mechanism of AMB action on the immune system is yet unknown. Because toxicity and limited solubility of AMB are likely to be responsible for these discrepancies, we synthesized a nontoxic derivative of AMB (AMBSH), and we investigated its immune modulating effects on murine B cells. Our results show that AMBSH induces a strong proliferative response under conditions where AMB is weakly efficient or toxic, and that AMBSH supports maturation to Ig secretion. When suboptimal doses of LPS (or BCGF) are present together with AMBSH, a synergistic effect on B cell proliferation occurs. Frequency analyses reveal that, although only a limited number of B cells respond to AMBSH alone, a large population of B cells will respond to subthreshold doses of LPS in the presence of this polyene. Finally, we show that incubation of spleen cells with AMBSH results in an increase in Ia expression. These results are discussed in terms of the membrane disorganizing properties of polyene antibiotics.