Increased cerebrospinal fluid osteopontin levels and its involvement in macrophage infiltration in neuromyelitis optica

Publication date: Available online 15 January 2015 Source:BBA Clinical Author(s): Yoshinobu Kariya , Yukiko Kariya , Toshie Saito , Shuhei Nishiyama , Takashi Honda , Keiko Tanaka , Mari Yoshida , Kazuo Fujihara , Yasuhiro Hashimoto 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. 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. These results indicate that osteopontin is involved in NMO pathology and thus therapeutic strategies that target osteopontin signaling may be useful to treat NMO.

Source: BBA Clinical - January 15, 2015 Category: Biochemistry Source Type: research