Schiffmann E, Geetha V, Pencev D, Warabi H, Mato J, Hirata F, Brownstein M, Manjunath R, Mukherjee A, Liotta L, Terranova V P
Agents Actions Suppl. 1983;12:106-20. doi: 10.1007/978-3-0348-9352-7_6.
PMNs upon stimulation by a chemoattractant adhere to a substratum and then in amoeboid fashion migrate toward the source of the attractant. We have studied molecular events in both adherence and migration and have arrived at the following conclusions: 1) PMNs, like other motile cells such as highly metastatic tumor cells, can use laminin to attach to Type IV basement membrane collagen. PMNs may use this anchoring mechanism in their emigration from the vasculature. 2) Attached cells may be stimulated to migrate as a result of the chemo-attractant-induced inactivation of lipomodulin, a natural inhibitor of phospholipase A2, an enzyme that may be essential for chemotaxis. 3) The substrate for this enzyme is generated by both the CDP-choline and transmethylation pathways. These pathways may be regulated by another enzyme, transglutaminase (TGase). 4) Natural substrates of TGase, such as uteroglobin, inhibit leukocyte chemotaxis, again suggesting a regulatory role for TGase in chemotaxis. 5) Tumor cells also produce inhibitors of chemotaxis. In addition to protecting the tumor from the host's phagocytes, these inhibitors may be related to normal modulators of cell motility. Therefore, determination of their mode of action could increase our understanding of this type of cell behavior.
多形核白细胞(PMNs)在趋化因子的刺激下会黏附于基质,然后以阿米巴样方式朝着趋化因子的来源迁移。我们研究了黏附与迁移过程中的分子事件,并得出以下结论:1)多形核白细胞与其他运动细胞(如高转移性肿瘤细胞)一样,可利用层粘连蛋白附着于IV型基底膜胶原蛋白。多形核白细胞在从脉管系统移出时可能利用这种锚定机制。2)由于趋化因子诱导脂调素失活,附着的细胞可能会受到刺激而迁移,脂调素是磷脂酶A2的天然抑制剂,而磷脂酶A2可能是趋化作用所必需的一种酶。3)该酶的底物由CDP - 胆碱和转甲基化途径生成。这些途径可能受另一种酶——转谷氨酰胺酶(TGase)的调节。4)转谷氨酰胺酶的天然底物,如子宫珠蛋白,可抑制白细胞趋化作用,这再次表明转谷氨酰胺酶在趋化作用中具有调节作用。5)肿瘤细胞也会产生趋化作用抑制剂。除了保护肿瘤免受宿主吞噬细胞的作用外,这些抑制剂可能与细胞运动的正常调节因子有关。因此,确定它们的作用方式可能会增进我们对这类细胞行为的理解。