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

BBA Clin. 2015 Jan 15;3:126-34. doi: 10.1016/j.bbacli.2015.01.003. eCollection 2015.

Kariya Y1, Kariya Y1, Saito T1, Nishiyama S2, Honda T3, Tanaka K4, Yoshida M5, Fujihara K2, Hashimoto Y1.

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.

CONCLUSION:

These results indicate that osteopontin is involved in NMO pathology.

GENERAL SIGNIFICANCE:

Thus therapeutic strategies that target osteopontin signaling may be useful to treat NMO.

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