Title |
Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils
|
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Published in |
PLOS ONE, January 2013
|
DOI | 10.1371/journal.pone.0054840 |
Pubmed ID | |
Authors |
Bit Na Kang, Sung Gil Ha, Nooshin S. Bahaie, M. Reza Hosseinkhani, Xiao Na Ge, Malcolm N. Blumenthal, Savita P. Rao, P. Sriramarao |
Abstract |
Association of the neurotransmitter serotonin (5-HT) with the pathogenesis of allergic asthma is well recognized and its role as a chemoattractant for eosinophils (Eos) in vitro and in vivo has been previously demonstrated. Here we have examined the regulation of 5-HT-induced human and murine Eos trafficking and migration at a cellular and molecular level. Eos from allergic donors and bone marrow-derived murine Eos (BM-Eos) were found to predominantly express the 5-HT2A receptor. Exposure to 5-HT or 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-HT2A/C selective agonist, induced rolling of human Eos and AML14.3D10 human Eos-like cells on vascular cell adhesion molecule (VCAM)-1 under conditions of flow in vitro coupled with distinct cytoskeletal and cell shape changes as well as phosphorylation of MAPK. Blockade of 5-HT2A or of ROCK MAPK, PI3K, PKC and calmodulin, but not G(αi)-proteins, with specific inhibitors inhibited DOI-induced rolling, actin polymerization and changes in morphology of VCAM-1-adherent AML14.3D10 cells. More extensive studies with murine BM-Eos demonstrated the role of 5-HT in promoting rolling in vivo within inflamed post-capillary venules of the mouse cremaster microcirculation and confirmed that down-stream signaling of 5-HT2A activation involves ROCK, MAPK, PI3K, PKC and calmodulin similar to AML14.3D10 cells. DOI-induced migration of BM-Eos is also dependent on these signaling molecules and requires Ca(2+). Further, activation of 5-HT2A with DOI led to an increase in intracellular Ca(2+) levels in murine BM-Eos. Overall, these data demonstrate that 5-HT (or DOI)/5-HT2A interaction regulates Eos trafficking and migration by promoting actin polymerization associated with changes in cell shape/morphology that favor cellular trafficking and recruitment via activation of specific intracellular signaling molecules (ROCK, MAPK, PI3K and the PKC-calmodulin pathway). |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 40 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 8 | 20% |
Researcher | 8 | 20% |
Student > Bachelor | 5 | 13% |
Student > Master | 5 | 13% |
Professor | 3 | 8% |
Other | 6 | 15% |
Unknown | 5 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 9 | 23% |
Immunology and Microbiology | 7 | 18% |
Medicine and Dentistry | 5 | 13% |
Biochemistry, Genetics and Molecular Biology | 2 | 5% |
Nursing and Health Professions | 1 | 3% |
Other | 5 | 13% |
Unknown | 11 | 28% |