title: Increased cerebrospinal fluid osteopontin levels and its involvement in macrophage infiltration in neuromyelitis optica.
abstract: BACKGROUND
  Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system that predominantly affects the optic nerves and spinal cord. Although NMO has long been considered a subtype of multiple sclerosis (MS), the effects of interferon-β treatment are different between NMO and MS. Recent findings of NMO-IgG suggest that NMO could be a distinct disease rather than a subtype of MS. However, the underlying molecular mechanism of NMO pathology remains poorly understood.
  
  
  METHODS
  OPN in the cerebrospinal fluid and brain of patients with NMO and with MS, as well as of patients with other neurologic disease/idiopathic other neurologic disease was examined using Western blotting, ELISA, immunohistochemistry and Boyden chamber.
  
  
  RESULTS
  Here we show that osteopontin is significantly increased in the cerebrospinal fluid of NMO patients compared with MS patients. Immunohistochemical analyses revealed that osteopontin was markedly elevated in the cerebral white matter of NMO patients and produced by astrocytes, neurons, and oligodendroglia as well as infiltrating macrophages. We also demonstrate that the interaction of the cerebrospinal fluid osteopontin in NMO patients with integrin αvβ3 promoted macrophage chemotaxis by activating phosphoinositide 3-kinase and MEK1/2 signaling pathways.
  
  
  CONCLUSIONS
  These results indicate that osteopontin is involved in NMO pathology.
  
  
  CONCLUSIONS
  Thus therapeutic strategies that target osteopontin signaling may be useful to treat NMO.
authors.affiliation: Department of Biochemistry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kariya
authors.affiliation: Department of Biochemistry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kariya
authors.affiliation: Department of Biochemistry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiyama
authors.affiliation: Department of Human Life Science, School of Nursing, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Neurology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.affiliation: Department of Biochemistry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
keywords: AQP4, aquaporin-4; Ab, antibody; Abs, antibodies; Biomarker; CNS, central nervous system; CSF, cerebrospinal fluid; Cerebrospinal fluid; EAE, experimental autoimmune encephalomyelitis; GFAP, glial fibrillary acidic protein; IFN, interferon; Integrin; MS, multiple sclerosis; Multiple sclerosis; NMO, neuromyelitis optica; Neuromyelitis optica; OPN, osteopontin; Osteopontin; PI3K, phosphoinositide 3-kinase; RGD, Arg–Gly–Asp; RGE, Arg–Gly–Glu; TRAP, tartrate-resistant form of acid phosphatase; mAb, monoclonal antibody; pAb, polyclonal antibody