Frankenburg S, Leibovici V, Mansbach N, Turco S J, Rosen G
Department of Dermatology, Hadassah University Hospital, Jerusalem, Israel.
J Immunol. 1990 Dec 15;145(12):4284-9.
Lipophosphoglycan (LPG) and glycosyl phosphatidylinositol Ag (GPI), are glycolipids present on the membrane of Leishmania parasites. Both glycolipids have been chemically characterized. LPG is a polysaccharide of repeating phosphorylated units linked to a phosphocarbohydrate core that is anchored to the membrane by lysoalkyl phosphatidylinositol (PI). The GPI are smaller glycolipids with a structure resembling the phosphocarbohydrate core of the LPG. They are anchored to the membrane by alkyl acyl PI. Their relative abundance, uniqueness of structure, and cellular location suggest a role in interactions of the parasites with host cells. In the present study we examined the effect of LPG and GPI on the activation of human peripheral blood monocytes. Three parameters were studied: the production of IL-1, chemotactic locomotion, and oxidative burst. We found that whereas neither GPI nor LPG directly affected monocyte activity, preincubation of the monocytes with LPG strongly inhibited further activation: The production of IL-1, after stimulation with LPS, was decreased in a dose-dependent manner. Previous incubation with LPG also inhibited chemotactic locomotion of monocytes and neutrophils in response to diacylglycerol, zymosan-activated serum, FMLP and LTB4. Luminol-dependent chemiluminiscence caused by stimulation of the monocytes with streptococci and histone was also inhibited. After fragmentation of the LPG into phosphoglycan and 1-O-alkylglycerol by phosphatidylinositol-phospholipase C, only the phosphoglycan retained inhibitory activity. No difference in inhibitory activity was found between LPG prepared from Leishmania major or Leishmania donovani promastigotes. These results show that the phosphoglycan of LPG inhibits the immunologic response of normal human monocytes and neutrophils, and suggest that LPG may influence the nature of the inflammatory response surrounding infected cells.
脂磷壁酸聚糖（LPG）和糖基磷脂酰肌醇抗原（GPI）是利什曼原虫寄生虫膜上存在的糖脂。这两种糖脂都已进行了化学表征。LPG是一种由重复的磷酸化单元组成的多糖，与一个磷酸碳水化合物核心相连，该核心通过溶烷基磷脂酰肌醇（PI）锚定在膜上。GPI是较小的糖脂，其结构类似于LPG的磷酸碳水化合物核心。它们通过烷基酰基PI锚定在膜上。它们的相对丰度、结构独特性和细胞定位表明它们在寄生虫与宿主细胞的相互作用中起作用。在本研究中，我们研究了LPG和GPI对人外周血单核细胞激活的影响。研究了三个参数：IL-1的产生、趋化运动和氧化爆发。我们发现，虽然GPI和LPG都不直接影响单核细胞活性，但单核细胞与LPG预孵育强烈抑制进一步激活：LPS刺激后IL-1的产生以剂量依赖方式减少。先前与LPG孵育也抑制了单核细胞和中性粒细胞对二酰甘油、酵母聚糖激活血清、FMLP和LTB4的趋化运动。用链球菌和组蛋白刺激单核细胞引起的鲁米诺依赖性化学发光也受到抑制。LPG被磷脂酰肌醇磷脂酶C切割成磷酸聚糖和1-O-烷基甘油后，只有磷酸聚糖保留了抑制活性。从硕大利什曼原虫或杜氏利什曼原虫前鞭毛体制备的LPG在抑制活性上没有差异。这些结果表明，LPG的磷酸聚糖抑制正常人单核细胞和中性粒细胞的免疫反应，并表明LPG可能影响感染细胞周围炎症反应的性质。
