Gastrin induces leukocyte-endothelial cell interactions in vivo and contributes to the inflammation caused by Helicobacter pylori.
Gastric mucosal inflammation causes hypergastrinemia, and gastrin receptors have been detected in several leukocyte types. We have analyzed whether gastrin affects the leukocyte-endothelial cell interactions in vivo by monitoring leukocyte rolling, adhesion, and emigration in rat mesenteric venules using intravital microscopy. Mesenteric superfusion with exogenous gastrin increased these processes in a concentration- and time-dependent manner, effects prevented by the cholecystokinin (CCK)-2 receptor antagonists (proglumide, L-365,260) but not by the CCK-1 receptor antagonist devazepide. A similar response was induced by exogenous CCK or endogenously released gastrin. CCK-2 receptors were localized in mesenteric macrophages and polymorphonuclear leukocytes. This effect of gastrin is not modulated by somatostatin and is independent of the endogenous release of histamine. To analyze whether hypergastrinemia elicited by Helicobacter pylori (HP) modulates the inflammation induced by the germ, rats were chronically administered with an extract of a CagA+/VacA+ strain of HP. This protocol increased gastrinemia and induced an inflammatory response in the rat mesentery. Blockade of CCK-2 receptors attenuated this response and induced a qualitative change in the leukocyte infiltrate suggestive of a receding inflammatory process. Our results reveal a new proinflammatory role of gastrin that seems to contribute to the maintenance of the inflammation elicited by HP components.
Alvarez
Angeles
A
Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Avd. Blasco Ibáñez 15, 46010-Valencia, Spain.
Ibiza
Sales
S
Hernández
Carlos
C
Alvarez-Barrientos
Alberto
A
Esplugues
Juan V
JV
Calatayud
Sara
S
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005755:Gastrins / Q000494:pharmacology*; D016481:Helicobacter Infections / Q000503:physiopathology*; D016480:Helicobacter pylori; D007249:Inflammation / Q000503:physiopathology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000382:microbiology / Q000503:physiopathology; D008642:Mesenteric Veins / Q000382:microbiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005755:Gastrins