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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.
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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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