Selective modulation of the expression of L-selectin ligands by an immune response

BACKGROUND: The adhesion molecule L-selectin is expressed on the cell surface of lymphocytes and mediates their migration from the bloodstream into lymph nodes. L-selectin is able to recognize four glycoprotein ligands, three of which--Sgp50, Sgp90, and Sgp200--are sulphated, bind specifically to L-selectin and are synthesized by the high endothelial venules of the peripheral and mesenteric lymph nodes. One of these three sulphated L-selectin ligands, Sgp90, has been shown to be identical to the known surface marker CD34 and is expressed on the cell surface of endothelial cells. The cDNA encoding Sgp50 has been cloned, and its product, which has been designated GlyCAM-1, is secreted. The third ligand, Sgp200, is both secreted and cell-associated. We have investigated how the expression of these sulphated glycoproteins is regulated during an immune response. RESULTS: Here we demonstrated that, during a primary immune response, the expression and secretion of both GlyCAM-1 and Sgp200 are reduced, recovering to normal levels 7-10 days after antigen stimulation. In contrast, the expression of cell-associated CD34 and Sgp200 is relatively unaffected. These results may account for the modest decreases in the binding of an L-selectin-IgG fusion protein to high endothelial venules of inflamed peripheral lymph nodes that have been observed after antigen exposure. In vivo experiments show that, following the decrease in the levels of secreted GlyCAM-1 and Sgp200, migration of lymphocytes from the blood stream into lymph nodes remains L-selectin-dependent, but more lymphocytes home to antigen-primed than unprimed peripheral lymph nodes. CONCLUSIONS: We suggest that the secreted forms of the L-selectin ligands GlyCAM-1 and Sgp200 act as modulators of cell adhesion, and that cell-associated CD34 and Sgp200 are the ligands that mediate the initial loose binding of lymphocytes to high endothelial venules

Factors associated with survival, laminitis and insulin dysregulation in horses diagnosed with equine pituitary pars intermedia dysfunction

Background: Pituitary pars intermedia dysfunction (PPID) is a commonly described endocrine disorder in higher latitudes of the Northern hemisphere but the description of the disease at lower latitudes and in the Southern hemisphere is limited. Objectives: Document the clinical features of PPID at different Australian latitudes and climates, and investigate factors associated with survival, laminitis and insulin dysregulation (ID). Study design: Retrospective study of 274 equids from eight institutions across Australia. Methods: A diagnosis of PPID was based on endogenous ACTH, overnight dexamethasone suppression test, thyrotropin-releasing hormone stimulation test or necropsy. Clinical and clinicopathologic characteristics of PPID and therapeutic responses were investigated. Laminitis was diagnosed by radiographic or histologic changes and ID was diagnosed based on endogenous insulin, an oral glucose test or a 2-step insulin-response test. Results: Being a pony, having a higher body condition score and pergolide administration were associated with survival. The clinical presentation of PPID changed with latitude and climate, with anhidrosis and polyuria/polydipsia more commonly recognised at lower latitudes. Laminitis was diagnosed in 89.9% of cases and ID was present in 76.5% of cases in which they were investigated. Main limitations: Despite the sample size, the lack of uniform testing at all locations (primary or referral cases) and the incompleteness of data sets limited the power of the statistical analyses. Conclusions: PPID can present with variable signs at different latitudes and climates, and ID should be investigated in equids diagnosed with PPID. Adequate body condition and administration of pergolide are fundamental in PPID management