Neale M L, Taylor K M, Matthews N
Dept. Medical Microbiology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Cytokine. 1991 May;3(3):250-6. doi: 10.1016/1043-4666(91)90024-8.
U937A cells are highly susceptible to tumor necrosis factor (TNF) cytolysis. They are also motile and incorporate fibronectin into the extracellular matrix (ECM). This takes the form of a dense fibrillar network in confluent cultures, but in sparse cultures appears as a "snail trail" of insolubilized fibronectin behind the moving cell. In contrast, U937A/R cells selected for resistance to TNF cytolysis are poorly motile and, although they synthesize fibronectin, fail to incorporate it into the ECM. Compared to U937A/R, U937A cells spread more rapidly and extensively on fibronectin-coated plastic and also bound 125I-fibronectin more effectively. Inhibition of U937A spreading on fibronectin required higher doses of GRGDSPK peptide, indicating greater expression on U937A of integrin-type, fibronectin receptors. Gangliosides are non-integrin structures which can bind fibronectin, and there were also qualitative and quantitative differences in ganglioside expression with U937A having two to five times more than U937A/R. Therefore the development of TNF resistance by U937A/R cells is accompanied by a reduced ability to interact with fibronectin, and this probably accounts for the reduced motility and inability to deposit fibronectin in the ECM.
U937A细胞对肿瘤坏死因子（TNF）介导的细胞溶解高度敏感。它们也具有运动性，并将纤连蛋白整合到细胞外基质（ECM）中。在汇合培养物中，这表现为密集的纤维状网络，但在稀疏培养物中，它表现为移动细胞后面不溶性纤连蛋白的“蜗牛轨迹”。相比之下，选择对TNF细胞溶解具有抗性的U937A/R细胞运动性较差，并且尽管它们合成纤连蛋白，但未能将其整合到ECM中。与U937A/R相比，U937A细胞在纤连蛋白包被的塑料上更快、更广泛地铺展，并且也更有效地结合125I-纤连蛋白。抑制U937A在纤连蛋白上的铺展需要更高剂量的GRGDSPK肽，这表明U937A上整合素型纤连蛋白受体的表达更高。神经节苷脂是非整合素结构，可以结合纤连蛋白，并且神经节苷脂表达在质量和数量上也存在差异，U937A的神经节苷脂表达比U937A/R多两到五倍。因此，U937A/R细胞对TNF抗性的发展伴随着与纤连蛋白相互作用能力的降低，这可能解释了其运动性降低以及无法将纤连蛋白沉积在ECM中的原因。
