The effect of
IS-741 (N-[(2-ethylsulfonylamino)-5-trifluoromethyl-3-pyridyl] cyclohexanecarboxamide monohydrate) on a model for
pancreatitis has been previously reported. Recent patho-histological observations of remedial tests using rats found that the
IS-741 administered group showed a low degree of tissue infiltration by inflammatory cells (polymorphonuclear leukocytes). We therefore examined cell adhesion, which is the first step in tissue infiltration by activated neutrophils, and investigated the effect of
IS-741 on cell adhesion between human umbilical vein endothelial cells (HUVEC) and human promyelo-
leukemia cell line (HL-60) cells during
lipopolysaccharide stimulation in vitro.
IS-741 significantly inhibited the adhesion of HL-60 cells to HUVEC. Further investigation of
IS-741 on individual cells revealed that
IS-741 mainly affected HL-60 cells. Investigation of the inhibitory effect of
IS-741 at the molecular level (targeting adhesion molecules) also revealed that
IS-741 had no effect on the appearance of
endothelial leukocyte adhesion molecule-1 (ELAM-1),
intercellular adhesion molecule-1 (ICAM-1) or
vascular cell adhesion molecule-1 (VCAM-1) on HUVEC, which supports the theory that
IS-741 is mainly effective on HL-60 cells, even at the molecular level. However, the inhibition of adhesion was noticed in experiments in which an anti-ICAM-1 or anti-VCAM-1 antibody was added to the adhesion test system. Therefore,
IS-741 is likely to affect adhesion molecules which belong to the beta1 or
beta2 integrin family.