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* Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021
The neurotransmitter serotonin (5-hydroxytryptamine (5-HT)) is implicated in enhancing inflammatory reactions of skin, lung, and gastrointestinal tract. To determine whether 5-HT acts, in part, through mast cells (MC), we first established that mouse bone marrow-derived MC (mBMMC) and human CD34+-derived MC (huMC) expressed mRNA for multiple 5-HT receptors. We next determined the effect of 5-HT on mouse and human MC degranulation, adhesion, and chemotaxis. We found no evidence that 5-HT degranulates MC or modulates IgE-dependent activation. 5-HT did induce mBMMC and huMC adherence to fibronectin; and immature and mature mBMMC and huMC migration. Chemotaxis was accompanied by actin polymerization. Using receptor antagonists and pertussis toxin, we identified 5-HT1A as the principal receptor mediating the effects of 5-HT on MC. mBMMC from the 5-HT1A receptor knockout mouse (5-HT1AR–/–) did not respond to 5-HT. 5-HT did induce accumulation of MC in the dermis of 5-HT1AR+/+ mice, but not in 5-HT1AR–/– mice. These studies are the first to demonstrate an effect of 5-HT on MC. Furthermore, both mouse and human MC respond to 5-HT through the 5-HT1A receptor. Our data are consistent with the conclusion that 5-HT promotes inflammation by increasing MC at the site of tissue injury.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the National Institute of Allergy and Infectious Diseases-National Institutes of Health Intramural Research Grant Program.
2 Address correspondence and reprint requests to Dr. Nataliya M. Kushnir-Sukhov, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C208, 10 Center Drive, MSC 1881, Bethesda, MD 20892-1881. E-mail address: nkushnir{at}niaid.nih.gov
3 Abbreviations used in this paper: MC, mast cell; 5-HT, 5-hydroxytryptamine; huMC, CD34+-derived human MC; mBMMC, mouse bone marrow-derived MC; HSA, human serum albumin; 
-hex, -hexosaminidase; pAb, polyclonal Ab; SCF, stem cell factor; LTB4, leukotriene B4; SERT, serotonin transporter.
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