5-hydroxytryptamine induces mast cell adhesion and migration.
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-HT(1A) as the principal receptor mediating the effects of 5-HT on MC. mBMMC from the 5-HT(1A) receptor knockout mouse (5-HT(1A)R(-/-)) did not respond to 5-HT. 5-HT did induce accumulation of MC in the dermis of 5-HT(1A)R(+/+) mice, but not in 5-HT(1A)R(-/-) 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-HT(1A) receptor. Our data are consistent with the conclusion that 5-HT promotes inflammation by increasing MC at the site of tissue injury.
Kushnir-Sukhov
Nataliya M
NM
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. nkushnir@niaid.nih.gov
Gilfillan
Alasdair M
AM
Coleman
John W
JW
Brown
Jared M
JM
Bruening
Sandra
S
Toth
Miklos
M
Metcalfe
Dean D
DD
D000199:Actins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D002448:Cell Adhesion; D015550:Cell Degranulation / Q000187:drug effects; D002465:Cell Movement; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D037342:Pertussis Toxin / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000199:Actins; D016207:Cytokines; D005353:Fibronectins; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D037342:Pertussis Toxin