Histamine involvement in UVB‐ and cis‐urocanic acid‐induced systemic suppression of contact hypersensitivity responses

Abstract

SUMMARYStudies in experimental models have implicated histamine and prostanoids in ultra-violet B ( UVB)-and cis-urocanic acid ( UCA)-induced systemic immunosuppression. This study examined the hypothesis that UVB irradiation and cis-UCA suppressed contact hypersensitivity responses to hapten by induction of histamine, which in turn evoked a prostanoid-dependent component of immunosuppression. BALB/c mice were administered with a cis-UCA monoclonal antibody, a combination of histamine types 1 and 2 receptor antagonists, or indomethacin. Mice were sensitized to 2,4,6-trinitrochlorobenzene (TNCB) on their ventral surface 5 days after UVB irradiation, or cis-UCA or histamine administration. Ears were challenged with TNCB 5 days later. Cis-UCA antibody inhibited the suppressive eÂects of UVB by approximately 60% and confirmed that suppression of contact hypersensitivity responses by UVB was due, at least in part, to mechanisms involving cis-UCA. Histamine suppressed contact hypersensitivity responses and the eÂects of cis-UCA and histamine were not cumulative, suggesting that cis-UCA and histamine signal largely through the same pathway. The immunosuppressive eÂects of histamine were not aÂected by the cis-UCA antibody, consistent with the model that histamine acts downstream of cis-UCA. Administration of histamine receptor antagonists and indomethacin each approximately halved the UVB-and cis-UCA-induced systemic suppression of contact hypersensitivity responses. The eÂects of the reagents that inhibited the action of histamine and prevented prostanoid production were not cumulative, and suggested involvement in the same pathway. These results support the involvement of cis-UCA, histamine and prostanoids, in a sequence, in UVB-induced systemic suppression of contact hypersensitivity responses. INTRODUCTIONwhich, in turn, initiates immunosuppressive signals. There is some evidence that DNA may be a UVB photoreceptor,6,7 Ultra-violet B ( UVB) irradiation (wavelength 280-320 nm) is but trans-urocanic acid (deaminated histidine), a molecular immunosuppressive and allows the growth of highly antigenic species located superficially in the stratum corneum of the skin UV-induced tumours.1,2 The immunosuppression can be both and which isomerizes to its cis form on UVB irradiation, has local and systemic, and results in reduced expression of contact also been implicated in the mechanisms whereby UV hypersensitivity (CHS) and delayed-type hypersensitivity irradiation generates systemic immunosuppression.8-12 Skin ( DTH) responses to a variety of antigens in mice and humans.painting or parenteral inoculation with cis-UCA can reduce Examination of the suppression of CHS responses to haptens systemic CHS responses and is associated with an alteration in experimental animals has allowed some dissection of the in antigen-presenting cell ability in vivo. However, in vitro mechanisms of the UVB-induced eÂects.2-4 studies have shown that the defect is not due to the direct As less than 10% of UVB irradiation reaches the dermis,5 eÂec...

Genetic control of susceptibility to UV-induced immunosuppression by interacting quantitative trait loci

“…Even after accounting for the effects at D14Mit260, however, the marker at D14Mit185 still appeared to have a significant effect on the trait. Because D14Mit260 (19.5 cM) and D14Mit185 (54 cM) are distant, there may be multiple loci on chromosome 14. However with the sample size available, this conclusion is speculative and it is not possible to resolve these two loci.…”

Effect of Both Ultraviolet B Irradiation and Histamine Receptor Function on Allergic Responses to an Inhaled Antigen

“…Histamine and its derivatives can act via the H2R to inhibit the immune response by the induction of T suppressor cell activity (35) and, in humans, have been shown to inhibit mixed T lymphocyte proliferation (36). More recently, in models of UVB control of contact hypersensitivity responses, H1R and H2R antagonists applied before and immediately after UVB irradiation partially reversed the effects of UVB (29). At the time, it was hypothesized that this modulation was a result of histamine binding to the H2R on dendritic cells and a subsequent increase in cAMP.…”

“…The radiation output for each experiment was measured using a UVX radiometer with a UVX-31 sensor (UV Products). As previously described (15,29), a 2 ϫ 4 cm dorsal patch of skin was cleanshaven. Mice were irradiated in 4 ϫ 6 cm compartments of a clear perspex box with wire mesh roofing and a polyvinylchloride plastic sheet (to remove wavelengths Ͻ290 nm) placed between the mice and UV lamps.…”

“…UVB irradiation of skin results in degranulation of mast cells and the release of histamine (28). Previous studies have demonstrated that the application of H1R and H2R antagonists before and after UVB irradiation partially reversed the immunosuppressive effects of UVB and cis-urocanic acid (29,30). To further examine the role of the H1R and H2R in UVB-induced immunosuppression, the papain-specific responses of these mice were investigated.…”

Primary Defect in UVB-Induced Systemic Immunomodulation Does Not Relate to Immature or Functionally Impaired APCs in Regional Lymph Nodes

“…Qualitative and quantitative changes in lymph node DCs of UVirradiated mice were examined in three experimental systems using mice irradiated 4 -5 days previously with 8 kJ/m 2 UVB, a dose consistently equal to 3-4 minimal erythemal doses (MED) in BALB/c mice (8,21). The first involved ventral application of the hapten, trinitrochlorobenzene (TNCB), and 18 h later, the harvest and culture of low density (DC-enriched) populations from the brachial, axillary, and inguinal lymph nodes; similar application of TNCB sensitized for a strong CHS response if reapplied to the ears 5 days later (8,21).…”