Neuropeptide-mediated regulation of hapten-specific IgE responses in mice II. Mechanisms of substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vitro

Abstract

Previous studies in our laboratory have shown that substance P (SP), injected into benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) sensitized mice at the peak of the benzylpenicilloyl (BPO)-specific IgE response, suppressed these responses in isotype-specific fashion within 48 h. These studies also showed that SP, but not neurotensin (NT), serotonin (5-HT), somatostatin (SOM) or gastrin, suppressed BPO-specific memory IgE antibody-forming cell (AFC) responses induced in vitro, also in isotype-specific fashion. To investigate the mechanisms by which SP suppressed BPO-specific IgE AFC responses were induced in vitro, these responses were induced by culturing spleen cells from BPO-KLH sensitized mice for 5 days with BPO-KLH with or without whole SP, amino terminal SP (SP 1–4: Arg-Lys-Pro-Lys), or carboxy terminal SP (SP 8–11: Phe-Gly-Leu-Met). In some experiments, the SP receptor antagonist ( d-Pro 2, d-Phe 7, d-Trp 9)-SP ( d-SP) was included in culture. In other experiments anti-interferon monoclonal antibody (anti-IFNγ mAb) was included in culture. Whole SP and SP 8–11, but not SP 1–4, suppressed BPO-specific IgE AFC responses induced in vitro. The suppression obtained was IgE isotype-specific and dose-dependent. Inclusion of SP receptor antagonist ( d-Pro 2, d-Phe 7, d-Trp 9)-SP inhibited suppression of BPO-specific memory IgE AFC responses by SP or SP 8–11. The SP-mediated suppression of BPO-specific memory IgE responses appeared to involve interferon gamma (IFNγ).