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The skin sites of the mouse where delayed-type hypersensitivity (DTH) reactions are most easily elicited (foot pads and ears) are particularly rich in 5-hydroxytryptamine (5-HT)-containing mast cells. Since mice are deficient in circulating basophils, which play a role in at least some DTH reactions, we investigated the possibility that the mast cells were playing an important role in the evolution of the skin reactions of DTH in mice. We found that reserpine, a drug which depletes mast cells of 5-HT, abolished the ability of the mouse to make DTH reactions in the skin. The suppressive effect of reserpine could be partially blocked by monoamine oxidase inhibitors which prevent the degradation of 5-HT in the cytosol of the mast cell. Spleen cells of immune, reserpine-treated mice transferred DTH reactions to nonimmune mice normally, indicating that the reserpine treatment did not affect immune T cells. DTH reactions could not be transferred into reserpine-treated mice. We suggest that T cells are continually emigrating from the blood, through postcapillary venule endothelium, by a mechanism which does not depend on vasoactive amines. If they are appropriately immune and meet the homologous antigen in the tissue, they induce mast cells to release vasoactive amines which cause postcapillary venule endothelial cells to separate, allowing the egress from the blood of cells which ordinarily do not recirculate. The secondarily arriving vasoactive amine-dependent cells are responsible for the micro- and macroscopic lesions of DTH reactions. Chemotactic factors may also be involved in bringing cells to the DTH reaction sites but we propose that T-cell regulation of vasoactive amine-containing cells allows the effector cells to pass through the endothelial gates after they are called.

Romney cross-bred wether lambs (aged 16-56 weeks and weighing 16-36 kg) were fed a concentrate diet ad lib. and surgically prepared with catheters in the left and right external iliac arteries and veins, inserted via the ipsilateral medial saphenous artery and vein. Sterile saline was continuously infused through all catheters and after appetite had fully recovered, bovine insulin was infused into one arterial catheter at rates of 5, 10 or 20 mU min-1 for periods of 15, 30 or 45 days in different lambs. At the end of the infusion the lambs were slaughtered to measure the composition of each hindquarter by tissue dissection and chemical analysis. As a result of the insulin infusions, plasma insulin concentrations were increased in venous blood sampled downstream from the infusion site and the arteriovenous concentration differences of glucose were greater across the treated than the contralateral limb. At the 10 and 20 mU min-1 infusion rates, systemic plasma insulin concentrations were increased and glucose concentrations decreased. Pooling results from all the treated lambs showed that intra-arterial insulin infusion increased weight of the hindquarter by 7%, weight of muscle by 5%, weight of dissected fat by 12% and weight of chemical fat by 11% when compared with the contralateral limb. No significant differences were detected among infusion rates or times of infusion. Much of the variation in response between lambs was negatively correlated to their age and/or liveweight when they entered the study. The results demonstrate that tissues in the hindlimb respond to local concentrations of a circulating hormone, provide strong evidence that insulin is an anabolic hormone in the growing postnatal lamb and suggest that such responses diminish with age.