{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:18:38Z","timestamp":1790965118002,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autoantibody neuromyelitis optica-IgG (NMO-IgG) recognizing aquaporin-4 (AQP4) is implicated as playing a central role in the physiopathology of NMO. The aim of this in vitro-based study was to characterize functional consequences of interaction between NMO-IgG and cells of the neurovascular unit (astrocytes and brain endothelium) that would provide insight into recognized features of NMO, namely altered blood-brain barrier (BBB) permeability and granulocyte recruitment. We used sera from NMO and longitudinally extensive transverse myelitis cases shown to bind in a characteristic perivascular pattern to primate cerebellar slices. Using flow cytometry, we found that sera from NMO-IgG-positive patients reacted with CNS-derived human fetal astrocytes, whereas sera from multiple sclerosis patients did not. We demonstrated that NMO-IgG binding to astrocytes alters aquaporin-4 polarized expression and increases permeability of a human BBB endothelium\/astrocyte barrier. We further demonstrated that NMO-IgG binding to human fetal astrocytes can result in NK cell degranulation, astrocyte killing by Ab-dependent cellular cytotoxicity and complement-dependent granulocyte attraction through the BBB model. Our study highlights important functional roles for NMO-IgG that could account for pathological lesions and BBB dysfunction observed in NMO.<\/jats:p>","DOI":"10.4049\/jimmunol.181.8.5730","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:47:01Z","timestamp":1397850421000},"page":"5730-5737","source":"Crossref","is-referenced-by-count":221,"title":["Functional Consequences of Neuromyelitis Optica-IgG Astrocyte Interactions on Blood-Brain Barrier Permeability and Granulocyte Recruitment"],"prefix":"10.1093","volume":"181","author":[{"given":"Thierry","family":"Vincent","sequence":"first","affiliation":[{"name":"Laboratoire d\u2019Immunologie, H\u00f4pital Saint-Eloi-CHU Montpellier , Montpellier,","place":["France"]},{"name":"Neuroimmunology Unit, and Experimental Therapeutics Program, Montreal Neurological Institute, McGill University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Saikali","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, and Experimental Therapeutics Program, Montreal Neurological Institute, McGill University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Cayrol","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Laboratory, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al\u2013Notre-Dame Hospital, Universit\u00e9 de Montr\u00e9al , Montr\u00e9al, Qu\u00e9bec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro D","family":"Roth","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, and Experimental Therapeutics Program, Montreal Neurological Institute, McGill University"},{"name":"Department of Biology, Faculty of Science, Universidad de Chile , Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Bar-Or","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, and Experimental Therapeutics Program, Montreal Neurological Institute, McGill University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Prat","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Laboratory, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al\u2013Notre-Dame Hospital, Universit\u00e9 de Montr\u00e9al , Montr\u00e9al, Qu\u00e9bec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack P","family":"Antel","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, and Experimental Therapeutics Program, Montreal Neurological Institute, McGill University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,10,15]]},"reference":[{"key":"2026012807141160000_R1","first-page":"805","article-title":"The spectrum of neuromyelitis optica","volume-title":"Lancet Neurol.","year":"2007"},{"key":"2026012807141160000_R2","first-page":"2106","article-title":"A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis","volume-title":"Lancet","year":"2004"},{"key":"2026012807141160000_R3","first-page":"473","article-title":"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012807141160000_R4","first-page":"935","article-title":"The role of aquaporin-4 in the blood-brain barrier development and integrity: studies in animal and cell culture models","volume-title":"Neuroscience","year":"2004"},{"key":"2026012807141160000_R5","first-page":"1085","article-title":"Three distinct roles of aquaporin-4 in brain function revealed by knockout mice","volume-title":"Biochim. Biophys. Acta","year":"2006"},{"key":"2026012807141160000_R6","first-page":"1","article-title":"Altered blood-brain barrier integrity in adult aquaporin-4 knockout mice","volume-title":"Neuroreport","year":"2008"},{"key":"2026012807141160000_R7","first-page":"143","article-title":"Plasma exchange for severe attacks of CNS demyelination: predictors of response","volume-title":"Neurology","year":"2002"},{"key":"2026012807141160000_R8","first-page":"128","article-title":"Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica","volume-title":"Mult. Scler.","year":"2007"},{"key":"2026012807141160000_R9","first-page":"878","article-title":"A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease","volume-title":"Ann. Neurol.","year":"1999"},{"key":"2026012807141160000_R10","first-page":"1450","article-title":"A role for humoral mechanisms in the pathogenesis of Devic\u2019s neuromyelitis optica","volume-title":"Brain","year":"2002"},{"key":"2026012807141160000_R11","first-page":"964","article-title":"Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression","volume-title":"Arch. Neurol.","year":"2006"},{"key":"2026012807141160000_R12","first-page":"1194","article-title":"Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis","volume-title":"Brain","year":"2007"},{"key":"2026012807141160000_R13","first-page":"1224","article-title":"Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis","volume-title":"Brain","year":"2007"},{"key":"2026012807141160000_R14","first-page":"1235","article-title":"Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre","volume-title":"Brain","year":"2007"},{"key":"2026012807141160000_R15","first-page":"7293","article-title":"Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury","volume-title":"J. Neurosci.","year":"1995"},{"key":"2026012807141160000_R16","first-page":"217","article-title":"Caspase 8 expression and signaling in Fas injury-resistant human fetal astrocytes","volume-title":"Glia","year":"2001"},{"key":"2026012807141160000_R17","first-page":"129","article-title":"B7 expression and antigen presentation by human brain endothelial cells: requirement for proinflammatory cytokines","volume-title":"J. Neuropathol. Exp. Neurol.","year":"2000"},{"key":"2026012807141160000_R18","first-page":"193","article-title":"The induction of ICAM-1 in human cerebromicrovascular endothelial cells (HCEC) by ischemia-like conditions promotes enhanced neutrophil\/HCEC adhesion","volume-title":"J. Neuroimmunol.","year":"1997"},{"key":"2026012807141160000_R19","first-page":"1377","article-title":"Ex vivo identification, isolation and analysis of tumor-cytolytic T cells","volume-title":"Nat. Med.","year":"2003"},{"key":"2026012807141160000_R20","first-page":"1220","article-title":"NKG2D-mediated cytotoxicity toward oligodendrocytes suggests a mechanism for tissue injury in multiple sclerosis","volume-title":"J. Neurosci.","year":"2007"},{"key":"2026012807141160000_R21","first-page":"45","article-title":"Statins reduce human blood-brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis","volume-title":"Ann. Neurol.","year":"2006"},{"key":"2026012807141160000_R22","first-page":"807","article-title":"Intercommunications between brain capillary endothelial cells and glial cells increase the transcellular permeability of the blood-brain barrier during ischaemia","volume-title":"J. Neurochem.","year":"2002"},{"key":"2026012807141160000_R23","first-page":"145","article-title":"Glial cell influence on the human blood-brain barrier","volume-title":"Glia","year":"2001"},{"key":"2026012807141160000_R24","first-page":"2221","article-title":"Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica","volume-title":"Neurology","year":"2007"},{"key":"2026012807141160000_R25","first-page":"108","article-title":"Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury","volume-title":"FASEB J.","year":"2007"},{"key":"2026012807141160000_R26","first-page":"1034","article-title":"Expression and function of water channels (aquaporins) in migrating malignant astrocytes","volume-title":"Glia","year":"2007"},{"key":"2026012807141160000_R27","first-page":"1674","article-title":"New possible roles for aquaporin-4 in astrocytes: cell cytoskeleton and functional relationship with connexin43","volume-title":"FASEB J.","year":"2005"},{"key":"2026012807141160000_R28","first-page":"202","article-title":"Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica","volume-title":"Nat. Clin. Pract. Neurol.","year":"2008"},{"key":"2026012807141160000_R29","first-page":"269","article-title":"Loss of aquaporin-4 in active perivascular lesions in neuromyelitis optica: a case report","volume-title":"Tohoku J. Exp. Med.","year":"2006"},{"key":"2026012807141160000_R30"},{"key":"2026012807141160000_R31","first-page":"97","article-title":"Complement expression on astrocytes and astrocytoma cell lines: failure of complement regulation at the C3 level correlates with very low CD55 expression","volume-title":"J. Neuroimmunol.","year":"1996"},{"key":"2026012807141160000_R32","first-page":"1485","article-title":"Revised diagnostic criteria for neuromyelitis optica","volume-title":"Neurology","year":"2006"},{"key":"2026012807141160000_R33","first-page":"2119","article-title":"C3a is a chemotaxin for human eosinophils but not for neutrophils. I. C3a stimulation of neutrophils is secondary to eosinophil activation","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026012807141160000_R34","first-page":"4708","article-title":"Deletion of the complement anaphylatoxin C3a receptor attenuates, whereas ectopic expression of C3a in the brain exacerbates, experimental autoimmune encephalomyelitis","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012807141160000_R35","first-page":"337","article-title":"Intimate cell conjugate formation and exchange of membrane lipids precede apoptosis induction in target cells during antibody-dependent, granulocyte-mediated cytotoxicity","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012807141160000_R36","first-page":"1535","article-title":"The immunologic release of constituents from neutrophil leukocytes. I. The role of antibody and complement on nonphagocytosable surfaces or phagocytosable particles","volume-title":"J. Immunol.","year":"1971"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/181\/8\/5730\/62581855\/7869.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/181\/8\/5730\/62581855\/7869.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:17:18Z","timestamp":1769602638000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/181\/8\/5730\/8009238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2008,10,15]]},"published-print":{"date-parts":[[2008,10,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.181.8.5730","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,10]]},"published":{"date-parts":[[2008,10]]}}}