Yamamoto N, Ngwenya B Z
Cancer Res. 1987 Apr 15;47(8):2008-13.
Cellular damage and inflammatory processes cause activation of phospholipase A in plasma membranes resulting in the production of various lysophospholipids. Treatment of mice with L-alpha-lysophosphatidylcholine, a decomposition product of phosphatidylcholine, greatly stimulates mouse peritoneal macrophages to ingest target cells via the Fc receptors. Similarly, treatment of mice with L-alpha-lysophosphatidylethanolamine and L-alpha-lysophosphatidyl-L-serine resulted in an enhanced ingestion activity of macrophages. Cancer cell membranes contain alkyl ether derivatives of phospholipids and neutral lipids. Inflamed cancer cells release decomposition products of alkyl ether phospholipids and neutral lipids, alkyl-lysophospholipids and alkylglycerols, respectively. Administration of alkyl ether analogues of lysophospholipids into mice were able to induce stimulation of macrophages for ingestion with Fc receptor preference. Two synthetic alkylglycerols, dodecylglycerol and tridecylglycerol, were tested. Dodecylglycerol induced an efficient stimulation of macrophages for Fc-mediated ingestion whereas tridecylglycerol induced a minimal level of activation. Therefore, in vivo effect of dodecylglycerol on macrophage stimulation is similar to that of lysophospholipids and their alkyl analogues. These in vivo stimulations of macrophages for Fc receptor-mediated ingestion activity were reproduced in in vitro activation of macrophages by treatment of peritoneal cells with the alkyl lipid derivatives. Among these compounds, dodecylglycerol was found to be the most potent agent for macrophage stimulation. Since macrophages are antigen-presenting cells, the degradation products of cancer cell membrane lipids may have immune potentiating capacity.
细胞损伤和炎症过程会导致质膜中的磷脂酶A激活，从而产生各种溶血磷脂。用磷脂酰胆碱的分解产物L-α-溶血磷脂酰胆碱处理小鼠，可极大地刺激小鼠腹腔巨噬细胞通过Fc受体摄取靶细胞。同样，用L-α-溶血磷脂酰乙醇胺和L-α-溶血磷脂酰-L-丝氨酸处理小鼠，可增强巨噬细胞的摄取活性。癌细胞膜含有磷脂和中性脂质的烷基醚衍生物。发炎的癌细胞分别释放烷基醚磷脂和中性脂质的分解产物，即烷基溶血磷脂和烷基甘油。将溶血磷脂的烷基醚类似物给予小鼠能够诱导巨噬细胞以Fc受体偏好性进行摄取刺激。测试了两种合成烷基甘油，十二烷基甘油和十三烷基甘油。十二烷基甘油可有效刺激巨噬细胞进行Fc介导的摄取，而十三烷基甘油诱导的激活水平最低。因此，十二烷基甘油对巨噬细胞刺激的体内作用类似于溶血磷脂及其烷基类似物。通过用烷基脂质衍生物处理腹膜细胞，在巨噬细胞的体外激活中重现了这些对巨噬细胞Fc受体介导的摄取活性的体内刺激。在这些化合物中，发现十二烷基甘油是刺激巨噬细胞最有效的试剂。由于巨噬细胞是抗原呈递细胞，癌细胞膜脂质的降解产物可能具有免疫增强能力。
