Modulation of murine peritoneal macrophage functions by gastrin.
The effect in vitro of gastrin-17 and gastrin-34 was studied at concentrations from 10(-12) to 10(-6) M on several functions of resting peritoneal macrophages from BALB/c mice: adherence to substrate, mobility (spontaneous and directed by chemical gradient or chemotaxis), and ingestion of inert particles (latex beads) or cells (Candida albicans). Both gastrins, at concentrations from 10(-10) to 10(-8) M, inhibited significantly all functions studied with the exception of adherence, which was increased. A dose-response relationship was observed, with a maximum inhibition of macrophage functions found at 10(-9) M. These peptides induced in murine macrophages a significant increase of cAMP levels at 60 and 120 s. Adenosine, an adenylate cyclase inhibitor, significantly increased the ingestion of latex beads, whereas the combined presence of adenosine and either G-17 or G-34 produced similar values to those of control samples without adenosine or gastrin. These results suggest that gastrin is a negative modulator of several macrophage functions, and that the inhibition of these activities is carried out through an increase of intracellular cAMP levels.
de la Fuente
M
M
Departamento de Biología Animal II (Fisiología Animal), Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Spain.
Drummond
J
J
del Rio
M
M
Carrasco
M
M
Hernanz
A
A
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002464:Cell Migration Inhibition; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005755:Gastrins / Q000494:pharmacology*; D007957:Leukocyte Adherence Inhibition Test; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects; D011498:Protein Precursors / Q000494:pharmacology*
D005755:Gastrins; D011498:Protein Precursors; C013706:big gastrin; C013550:gastrin 17; D000242:Cyclic AMP; D000241:Adenosine