title: Pannexin1 Channels Are Required for Chemokine-Mediated Migration of CD4+ T Lymphocytes: Role in Inflammation and Experimental Autoimmune Encephalomyelitis.
abstract: Pannexin1 (Panx1) channels are large high conductance channels found in all vertebrates that can be activated under several physiological and pathological conditions. Our published data indicate that HIV infection results in the extended opening of Panx1 channels (5-60 min), allowing for the secretion of ATP through the channel pore with subsequent activation of purinergic receptors, which facilitates HIV entry and replication. In this article, we demonstrate that chemokines, which bind CCR5 and CXCR4, especially SDF-1α/CXCL12, result in a transient opening (peak at 5 min) of Panx1 channels found on CD4(+) T lymphocytes, which induces ATP secretion, focal adhesion kinase phosphorylation, cell polarization, and subsequent migration. Increased migration of immune cells is key for the pathogenesis of several inflammatory diseases including multiple sclerosis (MS). In this study, we show that genetic deletion of Panx1 reduces the number of the CD4(+) T lymphocytes migrating into the spinal cord of mice subjected to experimental autoimmune encephalomyelitis, an animal model of MS. Our results indicate that opening of Panx1 channels in response to chemokines is required for CD4(+) T lymphocyte migration, and we propose that targeting Panx1 channels could provide new potential therapeutic approaches to decrease the devastating effects of MS and other inflammatory diseases.
authors.affiliation: Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103; Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103;
authors.forename: Stephani
authors.identifier: 0000-0002-1561-828X
authors.initials: S
authors.lastname: Velasquez
authors.affiliation: Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103; Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103;
authors.forename: Shaily
authors.identifier: 0000-0001-8407-1161
authors.initials: S
authors.lastname: Malik
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697; and.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lutz
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: Eliana
authors.identifier: 0000-0002-6650-3976
authors.initials: E
authors.lastname: Scemes
authors.affiliation: Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103; Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103; eliseo.eugenin@rutgers.edu.
authors.forename: Eliseo A
authors.initials: EA
authors.lastname: Eugenin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000276:immunology*; D017630:Connexins / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D013116:Spinal Cord
chemical_list: D054377:Chemokine CXCL12; D017630:Connexins; C515256:Cxcl12 protein, mouse; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; C503631:Panx1 protein, mouse; D000255:Adenosine Triphosphate