ANGIOPEPTIN, A SOMATOSTATIN-14 ANALOG, DECREASES ADHESIVENESS OF RAT LEUKOCYTES TO UNSTIMULATED AND IL-1-BETA-ACTIVATED RAT-HEART ENDOTHELIAL-CELLS

We have previously demonstrated that somatostatin-14 and its octapeptide analogue, angiopeptin, decrease the ability of rat heart endothelial cells to bind leukocytes [Leszczynski, et al., Reg. Pept. 43 (1993) 131-140]. Here, we examined whether exposure of leukocytes to angiopeptin modifies their adhesiveness to the unstimulated and to IL-1P-activated endothelium. Monolayers of unstimulated endothelial cells bind 274+/-12 leukocytes/mm(2). Exposure of leukocytes for 1, 4 and 24 hours to angiopeptin (1 mu M) reduced significantly (P<0.05) adhesion of leukocytes from 274+/-12 to 188+/-10, 185+/-8 and 172+/-3 cells/mm(2), respectively. Stimulation of endothelial cells with IL-1 beta (100U/ml) for 24 hours increased endothelial adhesiveness from 274+/-12 to 381+/-17 adhering leukocytes/mm(2). Exposure of leukocytes for 1, 4 and 24 hours to angiopeptin (1 mu M) reduced significantly (p<0.05) binding of leukocytes to IL-1 beta-activated endothelium from 381+/-17 to 237+/-8, 254+/-11 and 248+/-13 cells/mm(2), respectively. Angiopeptin had no effect on the expression of lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) by leukocytes, as assessed by now cytometry. This suggests that angiopeptin modulates adhesive properties of leukocytes by (1) altering the expression of other than LFA-1 adhesion molecule(s) and/or (2) modulating the affinity of adhesion molecule(s) expressed by leukocytes. In conclusion, our results demonstrate that angiopeptin reduces leukocyte adhesiveness to unstimulated and to IL-1 beta-activated endothelium. It suggests that angiopeptin may suppress immune response via modulation of the leukocyte-endothelial interaction.