M Miyasaka

High affinity binding of the leucocyte adhesion molecule L-selectin to 3′-sulphated-Lea and -Lex oligosaccharides and the predominance of sulphate in this interaction demonstrated by binding studies with a series of lipid-linked oligosaccharides

The binding of the leucocyte adhesion molecule L-selectin has been investigated toward several structurally defined lipid-linked oligosaccharides immobilized on silica gel chromatograms or plastic wells. In both assay systems the 3-sulphated Le(a)/Le(x) type tetrasaccharides [formula: see text] were more strongly bound than 3-sialyl analogues. A considerable binding was observed to the 3-sulphated oligosaccharide backbone in the absence of fucose but not to a 3-sialyl analogue or fuco-oligosaccharide analogues lacking sulphate or sialic acid. Affinity for other sulphated saccharides: 3-sulphoglucuronyl neolactotetraosyl ceramide and glycolipids with sulphate 3-linked to terminal or sub-terminal galactose or N-acetylgalactosamine was detected in the chromatogram assay only. These studies, together with earlier reports that L-selectin binding to endothelium is inhibited by sulphatide, highlight the relative importance of sulphate in the adhesive specificity of this protein.

The effect of anti-ICAM-1 monoclonal antibody treatment on the transplantation of the small bowel in rats

At present, organ transplantation has been conducted in various areas. But the most crucial problem is to find an efficient way to determine whether allograft rejection could be interfered by a novel approach, namely interference of adhesive interaction between cytotoxic cells and target organs with a monoclonal antibody (mAb) to intercellular adhesion molecule 1 (ICAM-1). We have studied the effect of anti-rat-ICAM-1 mAb on small bowel transplantation. Inbred Fischer and Lewis rats weighing 250 g were utilized. In allotransplantation, Fischer donor small bowel was transplanted to Lewis recipient. Group 1 consisted of untreated controls (n = 15). Group 2 was treated with the anti-ICAM-1 mAb (1 mg/kg/d intraperitoneally) for the first 5 days posttransplantation (n = 15). A dramatic inhibitory effect on allograft rejection was observed in the early stage of posttransplantation. On histological studies of grafted small intestine, group 2 showed normal morphological appearance while group 1 showed graft rejection until postoperative 5 days. However, changing around crypt cells and endothelial cells of microvasculature have appeared at 15 days of posttransplantation. These findings suggest that anti-ICAM-1 antibody is quite useful for delaying the occurrence of graft rejection in the early stage. Electron microscopic examination demonstrated the same results as conventional HE staining. Endothelial cells of the vessels and crypt cells may have an important role as target cells on graft rejection. Therefore, anti-ICAM-1 mAb may have potential as an alternative to conventional treatment for prevention of allograft rejection.

Prolongation of Rat Cardiac Allograft Survival by a Monoclonal Antibody: Anti-Rat Intercellular Adhesion Molecule-1

A mouse monoclonal antibody 1A29, which binds to the rat intercellular adhesion molecule-1 (ICAM-1), was studied for its effect on cardiac allograft survival. Expression of ICAM-1 was detectable only on vascular endothelium in normal heart, but was induced on myocardium associated with interstitial mononuclear cell infiltration during acute rejection. Treatment with monoclonal antibody 1A29 for 10 days after transplantation in 15 rats significantly prolonged allograft survival (mean(s.d.) 18(2) days; P<0.001), as compared with 15 isotype-matched control monoclonal antibody (mean(s.d.) 10(1) days) recipients. Five-day treatment with monoclonal antibody 1A29, when started at 5 days after transplantation (the time for which acute rejection is ongoing), also significantly extended the survival (mean(s.d.) 12(1) days; P<0.01) in seven rats. On histological examination, treatment with monoclonal antibody 1A29 reduced the degree of T-cell infiltration of both CD4+ and CD8+ subsets, and greatly reduced myocardial necrosis, vascular injury and intravenous thrombi. These results indicate that an anti-ICAM-1 monoclonal antibody can be used to prevent or treat acute rejection in the rat cardiac allograft model and suggest that human ICAM-1 is an important target for immunosuppression in clinical organ transplantation.