MHC class II molecules (Ia-antigens) on macrophages in BB/W rats.

The percentage, absolute number and expression of Ia-antigen of macrophages (Mø) in peripheral blood cells (PBC) and splenocytes from Bio-Breeding/Worcester (BB/W) rats were evaluated. The percentage of Mø in PBC and splenocytes from BB/W rats was significantly higher than those in normal Wistar rats from Clea Japan Inc. (NW/C) and Charles River Japan Inc. (NW/CR). The percentage of Ia-positive Mø in PBC and splenocytes from BB/W rats was significantly increased compared with that in NW/C rats. On the other hand, there was no significant difference in the percentage of Ia-positive Mø of PBC between BB/W and NW/CR rats, and the percentage of Ia-positive Mø in the spleen from BB/W rats was significantly lower than those in NW/CR rats. Thus, the quantity of MHC class II molecules on circulating Mø is not related to the pathogenesis of diabetes mellitus in BB/W rats.

Effects of cyclosporin A and insulin on peripheral lymphocytes in BB/W rats.

The effects of cyclosporin A (Cs-A) and insulin on peripheral lymphocytes in BB/W rats were studied. The cumulative incidence of overt diabetes in untreated BB/W rats was 72% up to 120 days of observation, whereas the incidence was 13% in Cs-A-treated rats. Lymphocytopenia, consisting of decreased OX19+ (pan T), W3/25+ (helper/inducer T) and OX8+ (cytotoxic/suppressor T) cells, was present in BB/W rats. Cs-A significantly decreased both the percentage and the absolute number of OX8+, OX6+ (Ia-positive) and OX12+ (B) cells, and augmented the ratio of W3/25+ to OX8+ cells in BB/W rats. On the other hand, insulin injection significantly decreased the percentage of OX6+ cells and the ratio of W3/25+ to OX8+ cells in BB/W rats. Thus, rearrangement of the ratio of helper/inducer T to cytotoxic/suppressor T cells and reduction in the number of Ia antigen-bearing cells could be important for the inhibitory effects of diabetes in BB/W rats upon treatment with Cs-A or insulin.

Glucose-induced production of type IV collagen and laminin P1 from cultured human umbilical vein endothelial cells.

To study the effect of high glucose on the production of type IV collagen and laminin P1 from the cultured human umbilical vein endothelial cells (HUVEC), we measured type N collagen and laminin P1 from HUVEC that were cultured under different conditions. The concentrations of type IV collagen in the cultured medium for high glucose (30 mM D-glucose) were significantly higher than those for low glucose (5.6 mM D-glucose), L-glucose (30 mM), or mannitol (30 mM). The increase of type IV collagen was dependent on the glucose concentration in the medium. The contents of type IV collagen in the cultured cells were also increased in high-glucose incubation compared with low glucose or L-glucose incubation. In contrast, the levels of laminin P1 in the medium cultured with high glucose were similar to those with low glucose or L-glucose. These results suggest that the increased production of type IV collagen may contribute to the thickening of basement membranes and may be linked to the development of diabetic nephropathy.