Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/ lpr mice had increased prevalence of CD4 + T cells in the spleen and liver and of TCR § g + B220 + cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.
Compared with normotensive mucosa, the portal hypertensive gastric mucosa has increased susceptibility to injury by noxious agents such as alcohol and aspirin, but the mechanism of this phenomenon is unclear. Since the microvasculature of the normal gastric mucosa is an important target of injury by these agents, we studied the histologic and ultrastructural features of gastric vasculature and mucosal microvasculature in rats with portal hypertension (produced by staged portal vein ligation) and in sham-operated rats. In portal hypertensive rats, the gastric mucosa was swollen and hyperemic and the endothelial cells of mucosal microvessels had very prominent enlarged cytoplasm obstructing capillary lumina. Quantitative analysis of transmission electron micrographs demonstrated that in portal hypertensive rats the gastric mucosal capillary endothelium had significantly increased cytoplasmic area (236%), increased pinocytic vesicular area (416%) and increased capillary basement membrane thickness (143%) compared to respective parameters in sham-operated control rats. Arterioles in the muscularis mucosae and in submucosa were thickened, and submucosal veins demonstrated features of arterialization. All these findings indicate that portal hypertension produces definite microvascular changes in the gastric mucosa resulting in compromise of the capillary lumina. These changes may be the basis for the observed morphologic and functional abnormalities of the portal hypertensive mucosa and its increased predisposition to injury.
Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham-operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24 +/- 5 vs 45 +/- 7 mm Hg PO2, P less than 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.