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脂肪酰麦芽糖的促有丝分裂、免疫佐剂及遗传学研究

Mitogenic, immunoadjuvancy, and genetic studies on fatty acyl maltose.

作者信息

Bissonnette E, Benrezzak O, Madarnas P, Brailovsky C, Nigam V N

机构信息

Département d'anatomie et de biologie cellulaire, Faculté de médecine, Université de Sherbrooke, Québec, Canada.

出版信息

Cancer Immunol Immunother. 1988;27(3):272-7. doi: 10.1007/BF00205451.

Abstract

Three synthetic glycolipids, maltose tetrapalmitate (MTP), maltose hexastearate (MHS), and maltose hexalinoleate (MHL) prepared as nontoxic lipid A analogs, and Escherichia coli lipopolysaccharide (LPS) were assayed for their mitogenic activity using spleen lymphocytes in nine inbred mouse strains and three F1 hybrids. The MTP and LPS were also assayed for their ability to enhance plaque-forming cell (PFC) responses using sheep red blood cells as the antigen in the same inbred mouse strains and F1 hybrids, The mitogenic activity of synthetic glyco-lipids was several fold lower than that of LPS and MHL was inferior to MTP and MHS. DBA/2J was the most responsive strain for MTP and DBA/1J and C3H/HeJ the least. The mitogenic activity of MTP was generally in agreement with the PFC response stimulation by it. Low-dose cyclophosphamide treatment of mice synergized MTP for PFC response augmentation. Genetic studies on MTP mitogenicity revealed that 90% of responder DBA/2J X nonresponder C3H/HeJ F1 hybrids had intermediate mitogenic activity. Among F2, 73% had intermediate-high activity and 27% were nonmitogenic. Among F1 X C3H/HeJ backcrosses 11% had high, 56% intermediate, and 33% had no mitogenic activity, whereas, for the F1 X DBA/2J backcross, 14% had high, 36% intermediate, and 50% low or negligible activity. The data favored a single gene for MTP activation of immune cells.

摘要

制备了三种合成糖脂,即麦芽糖四棕榈酸酯(MTP)、麦芽糖六硬脂酸酯(MHS)和麦芽糖六亚油酸酯(MHL)作为无毒脂多糖类似物,并使用九种近交系小鼠品系和三种F1杂种的脾淋巴细胞检测了它们与大肠杆菌脂多糖(LPS)的促有丝分裂活性。还使用绵羊红细胞作为抗原,在相同的近交系小鼠品系和F1杂种中检测了MTP和LPS增强空斑形成细胞(PFC)反应的能力。合成糖脂的促有丝分裂活性比LPS低几倍,且MHL不如MTP和MHS。DBA/2J是对MTP反应最强烈的品系,而DBA/1J和C3H/HeJ反应最弱。MTP的促有丝分裂活性通常与其对PFC反应的刺激作用一致。低剂量环磷酰胺处理小鼠可增强MTP对PFC反应的增强作用。对MTP促有丝分裂活性的遗传学研究表明,90%的反应性DBA/2J×无反应性C3H/HeJ F1杂种具有中等促有丝分裂活性。在F2代中,73%具有中等偏高活性,27%无促有丝分裂活性。在F1×C3H/HeJ回交后代中,11%具有高活性,56%具有中等活性,33%无促有丝分裂活性;而对于F1×DBA/2J回交后代,14%具有高活性,36%具有中等活性,50%具有低活性或可忽略不计的活性。这些数据支持免疫细胞的MTP激活由单个基因控制。

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