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Up-regulation of osteopontin and alphaBeta-crystallin in the normal-appearing white matter of multiple sclerosis: an immunohistochemical study utilizing tissue microarrays.

Sinclair C, Mirakhur M, Kirk J, Farrell M, McQuaid S

Neuropathology Laboratory, Institute of Pathology, Royal Group of Hospitals Trust, Belfast BT12 6BL, UK.

Tissue microarrays assembled from control and multiple sclerosis (MS) brain tissue have been used to assess the expression patterns and cellular distribution of two antigens, the proinflammatory cytokine osteopontin and the inducible heat shock protein alphaBeta-crystallin, which have previously been implicated in MS pathogenesis. Tissue cores were taken from paraffin-embedded donor blocks containing chronic active or chronic inactive plaques and normal-appearing white matter (NAWM) in seven MS cases, and white matter (WM) in five control cases. Expression patterns of both proteins were assessed against myelin density and microglial activation in the different tissue categories. Both proteins showed increased expression in all categories of MS tissue compared with control WM. The results indicate progressive up-regulation of expression of osteopontin with increased plaque activity, while elevation of alphaBeta-crystallin expression in MS tissue was independent of demyelination. In MS NAWM a significant correlation was observed between high levels of expression of osteopontin and alphaBeta-crystallin. Osteopontin expression was predominantly confined to astrocytes throughout MS tissues. alphaBeta-crystallin was expressed on astrocytes, oligodendrocytes and occasionally on demyelinated axons. Taken together, these data indicate a wider distribution of osteopontin and alphaBeta-crystallin in MS tissues than previously described and support their proposed role in MS pathogenesis.

Published 11 May 2005 in Neuropathol Appl Neurobiol, 31(3): 292-303.
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