Inhibition of allospecific response in pancreatic islet transplantation: the glycan approach.

UNLABELLED: Host resistance has precluded clinical islet transplantation from becoming a consistent therapy for type I diabetic patients, mainly due to both specific and nonspecific processes. O-glycosylated proteins have a primary role in immunologic synapses. Therefore, we investigated the effects of a putative immunomodulatory effect of the cleavage of these molecules on islet allotransplantation. METHODS: Murine islets were treated with O-sialoglycoprotein endopeptidase. Three endpoints were studied: (1) proliferation in allogeneic mixed islet mononuclear cell reactions using treated and control irradiated islets as stimulator cells of mononuclear cells; (2) expression of IA-d on monocytes using 48-hour transplants of treated versus control mouse islets into subcutaneous capsules; (3) posttransplant graft function in an in vivo model of islet allotransplantation. Treated and control islets were transplanted in diabetic mice treated daily with cyclosporine. Glycemia was monitored to determine diabetes reversion. RESULTS: The allogeneic proliferative response was maximal when allogeneic mononuclear cells were mixed with control islets; it was significantly decreased with treated islets. Mean proliferative inhibition rate of treated vs. control was 62%. IA-d expression on monocytes was maximal in control islets. Reversion was significantly different for treated versus control islets with its duration varied from 3 to 7 days. CONCLUSION: These results suggest that treatment of islets with O-sialoglycoprotein endopeptidase may modulate allogeneic immunologic reactions.

Effect of prenatal ethanol exposure on the growth of rat mandible skeletal units.

To study the effect of prenatal ethanol exposure on the growth of the skeletal units of the rat mandible, female Sprague-Dawley rats weighing 220-240 g were assigned to 1 of 3 different groups. One of the groups received ethanol in the drinking water (up to 10% v/v) for at least 15 days prior to mating, then 20% (v/v) throughout gestation. A balanced diet was supplied ad libitum. A second group was pair-fed with the first group. In addition, an amount of corn starch calorically equivalent to the amount of ethanol consumed by that group was offered. The remaining group formed the normal control and received food and water ad libitum. All groups were offered food and water ad libitum after delivery. Total caloric intakes in the first 2 groups. were 67.8% of that of the normal control group. The average off-spring weight at birth for rats given ethanol was 17% lower than that of normal control rats. There was no significant difference between the average weights of the offspring of pair-fed and normal control rats. During the ensuing 3 weeks, the weight of the offspring of alcoholic rats showed no indication of catching-up. All skeletal units of the mandible of the offspring of ethanol-treated females differed significantly from those of the control group. These differences varied between 2% and 16%. The skeletal units of mandibles of the pair-fed group did not differ significantly from ad libitum controls. The mandibular width was similar in all 3 experimental groups.