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Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils

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 tr...

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Autores principales: Kang, Bit Na, Ha, Sung Gil, Bahaie, Nooshin S., Hosseinkhani, M. Reza, Ge, Xiao Na, Blumenthal, Malcolm N., Rao, Savita P., Sriramarao, P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553162/
https://www.ncbi.nlm.nih.gov/pubmed/23372779
http://dx.doi.org/10.1371/journal.pone.0054840
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author Kang, Bit Na
Ha, Sung Gil
Bahaie, Nooshin S.
Hosseinkhani, M. Reza
Ge, Xiao Na
Blumenthal, Malcolm N.
Rao, Savita P.
Sriramarao, P.
author_facet Kang, Bit Na
Ha, Sung Gil
Bahaie, Nooshin S.
Hosseinkhani, M. Reza
Ge, Xiao Na
Blumenthal, Malcolm N.
Rao, Savita P.
Sriramarao, P.
author_sort Kang, Bit Na
collection PubMed
description 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).
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spelling pubmed-35531622013-01-31 Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils Kang, Bit Na Ha, Sung Gil Bahaie, Nooshin S. Hosseinkhani, M. Reza Ge, Xiao Na Blumenthal, Malcolm N. Rao, Savita P. Sriramarao, P. PLoS One Research Article 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). Public Library of Science 2013-01-23 /pmc/articles/PMC3553162/ /pubmed/23372779 http://dx.doi.org/10.1371/journal.pone.0054840 Text en © 2013 Kang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kang, Bit Na
Ha, Sung Gil
Bahaie, Nooshin S.
Hosseinkhani, M. Reza
Ge, Xiao Na
Blumenthal, Malcolm N.
Rao, Savita P.
Sriramarao, P.
Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils
title Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils
title_full Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils
title_fullStr Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils
title_full_unstemmed Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils
title_short Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils
title_sort regulation of serotonin-induced trafficking and migration of eosinophils
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553162/
https://www.ncbi.nlm.nih.gov/pubmed/23372779
http://dx.doi.org/10.1371/journal.pone.0054840
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