Journal article
Substance P and somatostatin can modulate the amount of IgG2a secreted in response to schistosome egg antigens in murine schistosomiasis mansoni
The Journal of immunology (1950), Vol.151(12), pp.6994-7004
1993
DOI: 10.4049/jimmunol.151.12.6994
PMID: 7505019
Abstract
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.
Details
- Title: Subtitle
- Substance P and somatostatin can modulate the amount of IgG2a secreted in response to schistosome egg antigens in murine schistosomiasis mansoni
- Creators
- Arthur M Blum - University of IowaAhmed Metwali - University of IowaRanjit C Mathew - Univ. Iowa coll. medicine, dep. internal medicine, div. gastroenterology-hepatology, Iowa City IA 52242, United StatesDavid Elliott - Univ. Iowa coll. medicine, dep. internal medicine, div. gastroenterology-hepatology, Iowa City IA 52242, United StatesJoel V Weinstock - Univ. Iowa coll. medicine, dep. internal medicine, div. gastroenterology-hepatology, Iowa City IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.151(12), pp.6994-7004
- Publisher
- American Association of Immunologists
- DOI
- 10.4049/jimmunol.151.12.6994
- PMID
- 7505019
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 1993
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984359814202771
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