title: Deficient p75 low-affinity neurotrophin receptor expression does alter the composition of cellular infiltrate in experimental autoimmune encephalomyelitis in C57BL/6 mice.
abstract: We have shown earlier that induction of experimental autoimmune encephalomyelitis (EAE)-a model for the human disease multiple sclerosis-in C57BL/6 wild-type mice resulted in the expression of the p75 low-affinity neurotrophin receptor (p75NTR) in endothelial cells in the CNS. In comparison to the clinical manifestation of EAE observed in wild-type C57BL/6 mice, C57BL/6 mice deficient for p75NTR (p75NTR knockout mice) developed a more severe or even lethal disease and concomitant increased levels of inflammation in the CNS. In order to elucidate the role of endothelial p75NTR in cellular infiltration under these pathological circumstances, we have performed a more detailed, quantitative examination of the composition of the cellular infiltrate invading the CNS in EAE wild-type and EAE p75NTR knockout mice. We compared spinal cords of EAE wild-type with those of EAE p75NTR knockout mice of the same clinical score (3.5) using immunohistochemical markers for the cell types present in the infiltratory cuffs in EAE: T-cells, B-cells, monocytes, microglia, resident and infiltrating macrophages and polymorphonuclear cells. Interestingly, we detected that the proportion of B-cells, cells of the monocyte-macrophage lineage and polymorphonuclear cells in the infiltratory cuff of EAE-p75NTR knockout mice was decreased at the account of the proportion of T-cells which appeared to be almost doubled in comparison to the EAE wild-type mice. The altered composition of the infiltrate in p75NTR deficient mice argues for an involvement of endothelial p75NTR in the interaction between the inflamed endothelium and the activated cells of the immune system, in particular the T-cells, in EAE.
authors.affiliation: Department of Medical Physiology, University Medical Centre Groningen, University of Groningen, A.Deusinglaan 1, 9713 AV Groningen KZ, Netherlands.
authors.forename: Britta
authors.initials: B
authors.lastname: Küst
authors.forename: Ietje
authors.initials: I
authors.lastname: Mantingh-Otter
authors.forename: Erik
authors.initials: E
authors.lastname: Boddeke
authors.forename: Sjef
authors.initials: S
authors.lastname: Copray
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005353:Fibronectins; D008840:Microfilament Proteins; D020800:Receptor, Nerve Growth Factor