De la Fuente M, Carrasco M, Hernanz A
Departamento de Fisiología Animal, Facultad de Ciencias Biológicas, Universidad Complutense, Madrid, Spain.
J Endocrinol. 1997 Jun;153(3):475-83. doi: 10.1677/joe.0.1530475.
We have studied the effects in vitro of gastrin-17 and gastrin-34, at concentrations from 10(-14) M to 10(-6) M, on several of the functions of peripheral blood human neutrophils, i.e. adherence to substrate, mobility (spontaneous and directed by a chemical gradient or chemotaxis), ingestion of inert particles (latex beads) and cells (Candida albicans) and superoxide anion production. Both gastrins inhibited several steps of the phagocytic process of human neutrophils, such as mobility and ingestion. By contrast, these peptides increased adherence and had no effect on superoxide anion production. In general, these effects were significant at peptide concentrations between 10(-12) M and 10(-8) M with a maximal effect at 10(-10) M. In addition, gastrin peptides induced a significant increase in intracellular cAMP levels at 30, 60 and 120 s. Moreover, the inhibitory effect of gastrin-17 on the ingestion capacity of neutrophils (latex bead phagocytosis) was similar to that obtained with EGTA, a well-known extracellular calcium chelating compound. Gastrin-17 was found to inhibit completely the stimulation of latex bead phagocytosis in neutrophils caused by the calcium ionophore A23187. These results suggest that gastrin is a negative modulator of the phagocytic process of human neutrophils, and that this effect might involve an increase in intracellular cAMP levels and a decrease in calcium entry into the cells.
我们研究了浓度在10^(-14) M至10^(-6) M之间的胃泌素-17和胃泌素-34对人外周血中性粒细胞多种功能的体外影响，即对底物的黏附、迁移（自发迁移以及由化学梯度引导的定向迁移或趋化作用）、惰性颗粒（乳胶珠）和细胞（白色念珠菌）的摄取以及超氧阴离子的产生。两种胃泌素均抑制人中性粒细胞吞噬过程的多个步骤，如迁移和摄取。相比之下，这些肽增加了黏附，并且对超氧阴离子的产生没有影响。一般来说，这些效应在肽浓度为10^(-12) M至10^(-8) M之间时显著，在10^(-10) M时达到最大效应。此外，胃泌素肽在30、60和120秒时诱导细胞内cAMP水平显著升高。而且，胃泌素-17对中性粒细胞摄取能力（乳胶珠吞噬作用）的抑制作用与用乙二醇双四乙酸（EGTA，一种著名的细胞外钙螯合剂）所获得的抑制作用相似。发现胃泌素-17完全抑制了钙离子载体A23187引起的中性粒细胞乳胶珠吞噬作用的刺激。这些结果表明，胃泌素是人类中性粒细胞吞噬过程的负调节因子，并且这种效应可能涉及细胞内cAMP水平的升高和细胞内钙内流的减少。
