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.
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-Pro2, D-Phe7, D-Trp9)-SP (D-SP) was included in culture. In other experiments anti-interferon monoclonal antibody (anti-IFN gamma mAb) was 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-Pro2, D-Phe7, D-Trp9)-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 (IFN gamma).
Carucci
J A
JA
Department of Pathology, State University of New York, Health Science Center at Brooklyn 11203.
Herrick
C A
CA
Durkin
H G
HG
D000595:Amino Acid Sequence; D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects*; D044482:Benzeneacetamides; D002478:Cells, Cultured; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010400:Penicillin G / Q000031:analogs & derivatives* / Q000276:immunology; D013373:Substance P / Q000494:pharmacology*
D044482:Benzeneacetamides; D007132:Immunoglobulin Isotypes; C015026:benzylpenicilloyl G; D013373:Substance P; D007073:Immunoglobulin E; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D010400:Penicillin G