Descoteaux A, Turco S J, Sacks D L, Matlashewski G
Institute of Parasitology, McGill University, Macdonald Campus, Ste-Anne de Bellevue, QC, Canada.
J Immunol. 1991 Apr 15;146(8):2747-53.
The effect of purified lipophosphoglycan (LPG) of Leishmania donovani on signal transduction and gene expression in murine bone marrow-derived macrophages was investigated. LPG stimulated the rapid expression of both c-fos and TNF genes within 30 min after exposure, suggesting that the interaction of LPG with its receptor stimulated a specific signal transduction pathway. Macrophages pretreated with LPG for 3 h became unresponsive to subsequent stimulation with LPS and the activators of protein kinase C, 1-oleoyl-2-acetyl-glycerol, and calcium ionophore A23187. Moreover, LPG induced a rapid down-modulation of TNF receptors. In contrast, the ability of macrophages to express the c-fos gene in response to the cAMP analogue, dibutyryl cAMP, was not impaired by LPG. Fragmentation of LPG revealed that the inhibitory activity of LPG required both the repeating phosphorylated disaccharides and the phosphosaccharide core. Collectively, these data demonstrate that LPG selectively impaired signal transduction in macrophages and suggest a role for this molecule in the survival of the parasite within the macrophage.
研究了杜氏利什曼原虫纯化脂磷壁酸聚糖（LPG）对小鼠骨髓来源巨噬细胞信号转导和基因表达的影响。LPG在暴露后30分钟内刺激c-fos和TNF基因快速表达，表明LPG与其受体的相互作用刺激了特定的信号转导途径。用LPG预处理3小时的巨噬细胞对随后的LPS以及蛋白激酶C激活剂1-油酰-2-乙酰甘油和钙离子载体A23187的刺激无反应。此外，LPG诱导TNF受体快速下调。相比之下，LPG并未损害巨噬细胞对cAMP类似物二丁酰cAMP反应时表达c-fos基因的能力。LPG片段化显示，LPG的抑制活性需要重复的磷酸化二糖和磷酸糖核心。总体而言，这些数据表明LPG选择性损害巨噬细胞中的信号转导，并提示该分子在寄生虫在巨噬细胞内的存活中起作用。
