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Research Article

GASTRIN INDUCES THE INTERACTION BETWEEN HUMAN MONONUCLEAR LEUKOCYTES AND ENDOTHELIAL CELLS THROUGH THE ENDOTHELIAL EXPRESSION OF P-SELECTIN AND VCAM-1

¹Universidad de Valencia ²University of Valencia

Submitted 23 February 2009 ; revised 23 September 2009 ; accepted in final form 2 October 2009

Gastric mucosal inflammation is frequently associated with hypergastrinemia, and a correlation exists between the level of gastrin and degree of gastritis. We have previously observed that gastrin promotes leukocyte-endothelial interactions and contributes to Helicobacter-induced inflammation in the rat mesentery. In the present study we aimed to evaluate a possible proinflammatory activity of gastrin in humans. Methods. The interaction between human leukocytes - U937 cells, peripheral blood polymorphonuclear (PMN), and mononuclear (PBMC) cells - and human umbilical vein endothelial cells (HUVEC) was analyzed in static and dynamic conditions. The endothelial expression of adhesion molecules (P-selectin, E-selectin, ICAM-1, VCAM-1) was analyzed by flow cytometry and fluorescent microscopy screening. Results. Gastrin increased the static adhesion of U937 cells to HUVEC (1h; 10^-9M: 122±9*%; 10^-8M: 143±17*%; 10^-7M: 162±14*% vs control, *P0.05). Incubation of HUVEC with gastrin (4h) also increased PBMC rolling (veh: 63±12; 10^-9M: 109±29; 10^-8M: 141±24; 10^-7M: 261±16* leuk/min, *P0.05) and adhesion (veh: 3±2, 10^-9M: 11±4*, 10^-8M: 17±5*, 10^-7M: 15±5* leuk/mm², *P0.05) in the parallel-plate flow chamber. Treatment of PBMC with gastrin had no effects. The CCK-2 receptor antagonist (L-365,260, 10^-7M) prevented the effects of gastrin. P-selectin and VCAM-1 expression were enhanced by gastrin, and neutralizing antibodies against these molecules prevented PBMC rolling and adhesion. Gastrin did not affect the interactions between HUVEC and PMN. Conclusions. Gastrin induces interactions between human mononuclear leukocytes and endothelial cells through the activation of CCK-2 receptor activation and the enhancement of endothelial P-selectin and VCAM-1.

CCK-2 receptors; endothelial adhesion molecules; leukocyte adhesion molecules; leukocyte-endothelial cell interactions