Shikama H, Yotsuya S, Satake S, Sugi H, Kato M
Central Research Institute, Ishihara Sangyo Kaisha, Ltd., Kusatsu, Shiga, Japan.
Biol Pharm Bull. 1999 Feb;22(2):127-31. doi: 10.1248/bpb.22.127.
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.
