PMID- 17922833 OWN - NLM STAT- MEDLINE DCOM- 20080327 LR - 20221109 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 123 IP - 3 DP - 2008 Mar TI - Neuropeptides activate human mast cell degranulation and chemokine production. PG - 398-410 AB - During neuronal-induced inflammation, mast cells may respond to stimuli such as neuropeptides in an FcepsilonRI-independent manner. In this study, we characterized human mast cell responses to substance P (SP), nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and compared these responses to human mast cell responses to immunoglobulin E (IgE)/anti-IgE and compound 48/80. Primary cultured mast cells, generated from CD34(+) progenitors in the presence of stem cell factor and interleukin-6 (IL-6), and human cultured mast cells (LAD2) were stimulated with these and other stimuli (gastrin, concanavalin A, radiocontrast media, and mannitol) and their degranulation and chemokine production was assessed. VIP and SP stimulated primary human mast cells and LAD cells to degranulate; gastrin, concanavalin A, radiocontrast media, mannitol, CGRP and NGF did not activate degranulation. While anti-IgE stimulation did not induce significant production of chemokines, stimulation with VIP, SP or compound 48/80 potently induced production of monocyte chemoattractant protein-1, inducible protein-10, monokine induced by interferon-gamma (MIG), RANTES (regulated on activation, normal, T-cell expressed, and secreted) and IL-8. VIP, SP and compound 48/80 also activated release of tumour necrosis factor, IL-3 and granulocyte-macrophage colony-stimulating factor, but not IL-4, interferon-gamma or eotaxin. Human mast cells expressed surface neurokinin 1 receptor (NK1R), NK2R, NK3R and VIP receptor type 2 (VPAC2) but not VPAC1 and activation of human mast cells by IgE/anti-IgE up-regulated expression of VPAC2, NK2R, and NK3R. These studies demonstrate the pattern of receptor expression and activation of mast cell by a host of G-protein coupled receptor ligands and suggest that SP and VIP activate a unique signalling pathway in human mast cells. These results are likely to have direct relevance to neuronally induced inflammatory diseases. FAU - Kulka, Marianna AU - Kulka M AD - National Research Council Canada, Room 432, 550 University Avenue, Charlottetown, PE, Canada. marianna.kulka@nrc-cnrc.gc.ca FAU - Sheen, Cecilia H AU - Sheen CH FAU - Tancowny, Brian P AU - Tancowny BP FAU - Grammer, Leslie C AU - Grammer LC FAU - Schleimer, Robert P AU - Schleimer RP LA - eng GR - R01 HL068546/HL/NHLBI NIH HHS/United States GR - R01 HL078860/HL/NHLBI NIH HHS/United States GR - R01HL078860/HL/NHLBI NIH HHS/United States GR - R01HL068546/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20071006 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Chemokines) RN - 0 (Elafin) RN - 0 (Neuropeptides) RN - 0 (PI3 protein, human) RN - 0 (Receptors, Neurokinin-1) RN - 0 (Receptors, Neuropeptide) RN - 0 (Tumor Necrosis Factor-alpha) RN - 33507-63-0 (Substance P) RN - 37221-79-7 (Vasoactive Intestinal Peptide) RN - 37341-29-0 (Immunoglobulin E) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) SB - IM MH - Calcitonin Gene-Related Peptide/immunology MH - Cell Degranulation/immunology MH - Cells, Cultured MH - Chemokines/*biosynthesis MH - Elafin/antagonists & inhibitors MH - GTP-Binding Proteins/antagonists & inhibitors MH - Humans MH - Immunoglobulin E/immunology MH - Mast Cells/*immunology MH - Nerve Growth Factor/immunology MH - Neuropeptides/*immunology MH - Receptors, Neurokinin-1/metabolism MH - Receptors, Neuropeptide/metabolism MH - Signal Transduction/immunology MH - Substance P/immunology MH - Tumor Necrosis Factor-alpha/biosynthesis MH - Vasoactive Intestinal Peptide/immunology PMC - PMC2433325 EDAT- 2007/10/10 09:00 MHDA- 2008/03/28 09:00 PMCR- 2009/03/01 CRDT- 2007/10/10 09:00 PHST- 2007/10/10 09:00 [pubmed] PHST- 2008/03/28 09:00 [medline] PHST- 2007/10/10 09:00 [entrez] PHST- 2009/03/01 00:00 [pmc-release] AID - IMM2705 [pii] AID - 10.1111/j.1365-2567.2007.02705.x [doi] PST - ppublish SO - Immunology. 2008 Mar;123(3):398-410. doi: 10.1111/j.1365-2567.2007.02705.x. Epub 2007 Oct 6.