Open AccessEphrin A Receptors and Ligands in Lesions and Normal‐Appearing White Matter in Multiple Sclerosis
Author(s) -
Sobel Raymond A.
Publication year - 2005
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2005.tb00098.x
Subject(s) - erythropoietin producing hepatocellular (eph) receptor , ephrin , multiple sclerosis , biology , white matter , pathology , axon guidance , receptor , neurodegeneration , lesion , neuroscience , axon , receptor tyrosine kinase , microbiology and biotechnology , medicine , signal transduction , immunology , magnetic resonance imaging , biochemistry , disease , radiology
Complexes of the tyrosine kinase ephrin ligands (ephrins) and their receptors (Ephs) provide critical cell recognition signals in CNS development. Complementary ephrin/Eph expression gradients present topographic guidance cues that may either stimulate or repulse axon growth. Some ephrin/Ephs are upregulated in adult CNS injury models. To assess their involvement in multiple sclerosis (MS), ephrin A1‐5 and Eph A1‐8 expression was analyzed in CNS tissues using immunohistochemistry. Control samples showed distinct expression patterns for each ephrin/Eph on different cell types. Perivascular mononuclear inflammatory cells, reactive astrocytes and macrophages expressed ephrin A1‐4, Eph A1, ‐A3, ‐A4, ‐A6 and ‐A7 in active MS lesions. Axonal ephrin A1 and Eph A3, ‐A4, and ‐A7 expression was increased in active lesions and was greater in normal‐appearing white matter (NAWM) adjacent to active lesions than within or adjacent to chronic MS lesions, in contralateral NAWM, or in control samples. As in development, therefore, there are temporally dynamic, lesion‐associated axonal ephrin/Eph A expression gradients in the CNS of MS patients. These results indicate that ephrin/Eph As are useful cell markers in human CNS tissue samples; they likely are involved in the immunopathogenesis of active lesions and in neurodegeneration in MS NAWM; and they represent potential therapeutic targets in MS.