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Anti‐inflammatory activity of nerve growth factor in experimental autoimmune encephalomyelitis: inhibition of monocyte transendothelial migration
Author(s) -
Flügel Alexander,
Matsumuro Kenji,
Neumann Harald,
Klinkert Wolfgang E.F.,
Birnbacher Robert,
Lassmann Hans,
Otten Uwe,
Wekerle Hartmut
Publication year - 2001
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/1521-4141(200101)31:1<11::aid-immu11>3.0.co;2-g
Subject(s) - experimental autoimmune encephalomyelitis , nerve growth factor , immunology , monocyte , biology , cytokine , myelin basic protein , encephalomyelitis , inflammation , receptor , myelin , endocrinology , central nervous system , multiple sclerosis , biochemistry
Abstract In order to analyze a putative immunomodulatory effect of NGF in experimental autoimmune encephalomyelitis (EAE) of the Lewis rat, we transduced myelin basic protein (MBP)‐specific CD4 + T cells with a recombinant retrovirus encoding NGF. These T MBP NGF cells secreted high levels of NGF, along with an unaltered Th1‐like cytokine pattern. Transfer studies showed that T MBP NGF cells were unable to mediate clinical EAE, when transferred alone, and, more important, they efficiently suppressed induction of clinical EAE by non‐transduced MBP‐specific T cells (T MBP cells). In contrast, NGF transduced ovalbumin‐specific T cells, which secreted high NGF levels, did not affect EAE induction. Suppression of clinical EAE by T MBP NGF cells was associated with a general reduction of inflammatory CNS infiltrates, with a most pronounced decrease of the monocyte/macrophage component. Using a culture model of the endothelial blood‐brain barrier (BBB), we found that NGF directly acts on blood‐derived monocytes via the p75 NGF receptor, thus interfering with monocyte migration through the activated BBB endothelium. Our data establish NGF as an anti‐inflammatory mediator interfering with T cell mediated autoimmune disease in the CNS. They further point to monocyte migration through blood vascular endothelium as one possible mechanism of NGF action.