Fidler I J, Nii A, Utsugi T, Brown D, Bakouche O, Kleinerman E S
Department of Cell Biology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Lymphokine Res. 1990 Winter;9(4):449-63.
The purpose of these studies was to determine whether the tumoricidal phenotype of human blood monocytes would be affected by different activation signals. Human monocytes obtained by elutriation of buffy coats were cultured in vitro in medium containing LPS, muramyltripeptide phosphatidylethanolamine (MTP-PE), or a lipopeptide analogue of gram-negative bacteria cell wall. These immunomodulators were added to monocytes in the presence or absence of IFN-gamma. Incubation with LPS, lipopeptide, and MTP-PE rendered the monocyte cytotoxic against allogeneic melanoma cells. Monocytes treated with LPS and lipopeptide (in the absence of IFN-gamma) secreted IL 1, TNF, and PGE2. In contrast, monocytes incubated with MTP-PE (in the absence of IFN-gamma) secreted only TNF. When the monocytes were coincubated with IFN-gamma (human but not mouse) and the immunomodulators, IL 1, TNF, and PGE2 were secreted at all test groups. These data show that some immunomodulators can regulate the release of TNF independently of IL 1 and that not all "activated tumoricidal macrophages" share identical phenotypes.
这些研究的目的是确定人血单核细胞的杀肿瘤表型是否会受到不同激活信号的影响。通过血沉棕黄层淘洗获得的人单核细胞在含有脂多糖(LPS)、胞壁酰三肽磷脂酰乙醇胺(MTP-PE)或革兰氏阴性菌细胞壁脂肽类似物的培养基中进行体外培养。这些免疫调节剂在有或无γ干扰素(IFN-γ)的情况下添加到单核细胞中。用LPS、脂肽和MTP-PE孵育使单核细胞对同种异体黑色素瘤细胞具有细胞毒性。用LPS和脂肽处理的单核细胞(在无IFN-γ的情况下)分泌白细胞介素1(IL 1)、肿瘤坏死因子(TNF)和前列腺素E2(PGE2)。相比之下,用MTP-PE孵育的单核细胞(在无IFN-γ的情况下)仅分泌TNF。当单核细胞与IFN-γ(人而非小鼠的)和免疫调节剂共同孵育时,所有测试组均分泌IL 1、TNF和PGE2。这些数据表明,一些免疫调节剂可独立于IL 1调节TNF的释放,且并非所有“活化的杀肿瘤巨噬细胞”都具有相同的表型。