title: Decreased sensitivity of atopic mononuclear cells to prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2).
abstract: The effect of PGE2 and PGD2 on several lymphocyte functions in vitro was evaluated in nonatopic and atopic subjects. Both PGE2 and PGD2 inhibited phytohemagglutinin-induced protein synthesis ([3H] leucine uptake) by nonatopic mononuclear cells and T cells in a dose-dependent manner (10(-6) to 10(-12) M). Protein synthesis by atopic mononuclear cells was not significantly suppressed by the above concentration of PGE2. Although PGD2 effectively suppressed protein synthesis by atopic mononuclear cells and T cells at 10(-6) M, lower concentrations were ineffective. Kinetic studies revealed significant differences in the suppressive effects of PGE2 and PGD2 on atopic and nonatopic mononuclear cells at 24 and 48 h, but not at 72 or 96 hr. Protein synthesis by T helper-enriched populations (suppressor cell depletion by anti-Leu-2b + complement) obtained from nonatopics was significantly reduced by PGE2 and PGD2, suggesting that these mediators may be directly inhibiting the responding population. By contrast, protein synthesis by T suppressor-enriched populations (helper cell depletion by OKT4 + complement) obtained from nonatopics was enhanced by PGE2 and PGD2, suggesting that the PG were activating these cells. Atopic T helper and T suppressor cells exhibited decreased responsiveness to PGE2 and PGD2 compared with nonatopic cells. PGE2 and PGD2 inhibited the phytohemagglutinin-stimulated proliferative response ([3H]thymidine uptake) by both atopic and nonatopic mononuclear cells in a dose-dependent manner and to the same extent. However, although PGE2 and PGD2 generated functional suppressor activity (when using a coculture technique) in nonatopic mononuclear cells, these mediators failed to activate atopic suppressor cells. These results suggest that reduced responses by atopic T cells to signals provided by PGE2 and PGD2 are not solely restricted to suppressor cell function, and could indicate an impaired ability to regulate immune and/or inflammatory reactions.
authors.forename: R E
authors.initials: RE
authors.lastname: Rocklin
authors.forename: L
authors.initials: L
authors.lastname: Thistle
authors.forename: C
authors.initials: C
authors.lastname: Audera
mesh_terms: D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology*; D014176:Protein Biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D011457:Prostaglandins D; D011458:Prostaglandins E; D004247:DNA; D015232:Dinoprostone; D015230:Prostaglandin D2