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.
Blum
A M
AM
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Metwali
A
A
Mathew
R C
RC
Elliott
D
D
Weinstock
J V
JV
D000818:Animals; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D000954:Antigens, Surface; D001667:Binding, Competitive; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008808:Mice, Inbred CBA; D010063:Ovum / Q000276:immunology; D018040:Receptors, Neurokinin-1 / Q000276:immunology; D011994:Recombinant Proteins; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013004:Somatostatin / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013373:Substance P / Q000494:pharmacology*; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D000954:Antigens, Surface; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D018040:Receptors, Neurokinin-1; D011994:Recombinant Proteins; D018800:Thy-1 Antigens; D013373:Substance P; D013004:Somatostatin; D007371:Interferon-gamma