Cutting edge: serotonin is a chemotactic factor for eosinophils and functions additively with eotaxin.
Elevated levels of serotonin (5-hydroxytryptamine, 5-HT) are observed in the serum of asthmatics. Herein, we demonstrate that 5-HT functions independently as an eosinophil chemoattractant that acts additively with eotaxin. 5-HT2A receptor antagonists (including MDL-100907 and cyproheptadine (CYP)) were found to inhibit 5-HT-induced, but not eotaxin-induced migration. Intravital microscopy studies revealed that eosinophils roll in response to 5-HT in venules under conditions of physiological shear stress, which could be blocked by pretreating eosinophils with CYP. OVA-induced pulmonary eosinophilia in wild-type mice was significantly inhibited using CYP alone and maximally in combination with a CCR3 receptor antagonist. Interestingly, OVA-induced pulmonary eosinophilia in eotaxin-knockout (Eot-/-) mice was inhibited by treatment with the 5-HT2A but not CCR3 receptor antagonist. These results suggest that 5-HT is a potent eosinophil-active chemoattractant that can function additively with eotaxin and a dual CCR3/5-HT2A receptor antagonist may be more effective in blocking allergen-induced eosinophil recruitment.
Boehme
Stefen A
SA
La Jolla Institute for Molecular Medicine, San Diego, CA 92121, USA.
Lio
Francisco M
FM
Sikora
Lyudmila
L
Pandit
Terlika S
TS
Lavrador
Karine
K
Rao
Savita P
SP
Sriramarao
P
P
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000502:physiology*; D000485:Allergens / Q000008:administration & dosage; D002464:Cell Migration Inhibition; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002631:Chemotactic Factors, Eosinophil / Q000037:antagonists & inhibitors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003533:Cyproheptadine / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D005464:Fluorobenzenes / Q000494:pharmacology; D006801:Humans; D036904:Leukocyte Rolling / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000485:Allergens; C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D005464:Fluorobenzenes; D010880:Piperidines; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D003533:Cyproheptadine; D012701:Serotonin; C079049:volinanserin