Substance P and somatostatin can modulate the amount of IgG2a secreted in response to schistosome egg antigens in murine schistosomiasis mansoni.
Substance P (SP) and somatostatin 1-14 (SOM) have immunoregulatory properties. Cells within the granulomas of murine schistosomiasis mansoni make both. SP enhances, whereas SOM inhibits soluble egg Ag (SEA)-induced, IFN-gamma production. IFN-gamma is important during IgG2a isotype switching. Thus, we investigated whether SP or SOM could affect IgG2a production in murine schistosomiasis. Our results show that SEA and rIFN-gamma stimulate splenic IgG2a secretion in murine schistosomiasis. Moreover, SP at > or = to 10(-10) M substantially increased both polyclonal as well as SEA-specific, IgG2a secretion from spleen cells challenged with SEA. However, cells exposed to SOM at > or = 10(-10)M showed strong inhibition. Also, both SP and SOM modulated the frequency of IgG2a-producing cells. Splenic IgG2a production in response to SEA, SP, and SOM required the presence of Thy 1.2+ cells, whereas, rIFN-gamma- induced IgG2a synthesis did not. Also, experiments using irradiation lymphocytes showed that SP, SOM, or rIFN-gamma modulation of IgG2a release was not dependent on cell proliferation. The highly specific SP receptor antagonist, CP-96,345, completely inhibited the effect of SP but not SOM on IgG2a release. This suggests that SP acted through an authentic NK-1 receptor and that SOM required a different receptor interaction. Granuloma cells secreted IgG2a constitutively. Yet, neither SEA, SP, SOM, rIFN-gamma, nor blocking anti-IFN-gamma mAb could modulate this constitutive IgG2a release during short term culture conditions. Moreover, the IgG2a secretion also continued in the absence of Thy 1.2+ lymphocytes. However, mice treated with CP-96,345 or octreotide (SOM agonist) in vivo produced granulomas that made little or no IgG2a. Spleen cell experiments showed that SEA, SP, SOM, and rIFN-gamma could only affect SEA-induced, IgG2a production during early stages of Ag stimulation. Thus, unlike the spleen, it is probable that the granulomas contain mostly activated B cells that have completed switch recombination.[1]References
- Substance P and somatostatin can modulate the amount of IgG2a secreted in response to schistosome egg antigens in murine schistosomiasis mansoni. Blum, A.M., Metwali, A., Mathew, R.C., Elliott, D., Weinstock, J.V. J. Immunol. (1993) [Pubmed]
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