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APOE ε3 attenuates experimental autoimmune neuritis by modulating T cell, macrophage and Schwann cell functions.
Exp Neurol. 2011 Aug; 230(2):197-206.EN

Abstract

Human apolipoprotein E (apoE) is a 34.2kDa glycosylated protein with three isoforms (apoE2, apoE3 and apoE4). Experimental autoimmune neuritis (EAN), an animal model for human Guillain-Barré syndrome, is an immune-mediated experimental disorder of the peripheral nervous system (PNS). Increased susceptibility to EAN in apoE deficient mice has been previously found. To elucidate the isoform-dependent effects of apoE on EAN, we used human apoE2, E3 and E4 transgenic mice (Tg) immunized with P0 peptide 180-199, as well as T cell proliferation test, macrophage and Schwann cell (SC) cultures to investigate the effects of apoE isoforms on the functions of T cells, macrophages and SCs both under naïve conditions and in EAN. Clinical signs of EAN were most severe in wild type (WT) C57BL/6 mice and apoE4 Tg mice, followed by apoE2 Tg mice and apoE3 Tg mice (WT≈E4>E2>E3, p<0.01). At the nadir of EAN, spleen weight and lymphocyte proliferation were in line with the clinical severity of the disease. Proliferation tests of purified T cells from naive mice stimulated with phytohemagglutinin or interleukin-12 showed isoform-specific differences (WT≈E4>E3≈E2, p<0.01). Macrophages from both naïve and EAN mice produced nitric oxide upon inflammatory stimulation with lipopolysaccharide, interferon-γ, polyinosinic:polycytidylic acid or combinations thereof, in an isoform-dependent manner (WT≈E4>E2>E3, p<0.01). Generalized intervention with 1400W, a specific inducible nitric oxide synthase inhibitor, significantly suppressed the clinical course of EAN in apoE2, E3 and E4 Tg mice and in WT mice. During the recovery stage of disease, the highest expression of CD178 (FasL) on SCs was found in apoE3 Tg mice. Our data support an isoform-dependent effect of apoE on EAN. This might be due to the isoform-specific effects of apoE on functions of T cells, macrophages and SCs, which contribute to the distinct clinical courses of EAN. ApoE3 might not only inhibit the onset and suppress the clinical severity of EAN, but also enhance the termination of immune responses in the PNS.

Authors+Show Affiliations

Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21550340

Citation

Zhang, Hong-Liang, et al. "APOE Ε3 Attenuates Experimental Autoimmune Neuritis By Modulating T Cell, Macrophage and Schwann Cell Functions." Experimental Neurology, vol. 230, no. 2, 2011, pp. 197-206.
Zhang HL, Mao XJ, Zhang XM, et al. APOE ε3 attenuates experimental autoimmune neuritis by modulating T cell, macrophage and Schwann cell functions. Exp Neurol. 2011;230(2):197-206.
Zhang, H. L., Mao, X. J., Zhang, X. M., Li, H. F., Zheng, X. Y., Adem, A., Mix, E., & Zhu, J. (2011). APOE ε3 attenuates experimental autoimmune neuritis by modulating T cell, macrophage and Schwann cell functions. Experimental Neurology, 230(2), 197-206. https://doi.org/10.1016/j.expneurol.2011.04.016
Zhang HL, et al. APOE Ε3 Attenuates Experimental Autoimmune Neuritis By Modulating T Cell, Macrophage and Schwann Cell Functions. Exp Neurol. 2011;230(2):197-206. PubMed PMID: 21550340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - APOE ε3 attenuates experimental autoimmune neuritis by modulating T cell, macrophage and Schwann cell functions. AU - Zhang,Hong-Liang, AU - Mao,Xi-Jing, AU - Zhang,Xing-Mei, AU - Li,Hai-Feng, AU - Zheng,Xiang-Yu, AU - Adem,Abdu, AU - Mix,Eilhard, AU - Zhu,Jie, Y1 - 2011/04/30/ PY - 2011/03/01/received PY - 2011/04/01/revised PY - 2011/04/17/accepted PY - 2011/5/10/entrez PY - 2011/5/10/pubmed PY - 2011/8/16/medline SP - 197 EP - 206 JF - Experimental neurology JO - Exp Neurol VL - 230 IS - 2 N2 - Human apolipoprotein E (apoE) is a 34.2kDa glycosylated protein with three isoforms (apoE2, apoE3 and apoE4). Experimental autoimmune neuritis (EAN), an animal model for human Guillain-Barré syndrome, is an immune-mediated experimental disorder of the peripheral nervous system (PNS). Increased susceptibility to EAN in apoE deficient mice has been previously found. To elucidate the isoform-dependent effects of apoE on EAN, we used human apoE2, E3 and E4 transgenic mice (Tg) immunized with P0 peptide 180-199, as well as T cell proliferation test, macrophage and Schwann cell (SC) cultures to investigate the effects of apoE isoforms on the functions of T cells, macrophages and SCs both under naïve conditions and in EAN. Clinical signs of EAN were most severe in wild type (WT) C57BL/6 mice and apoE4 Tg mice, followed by apoE2 Tg mice and apoE3 Tg mice (WT≈E4>E2>E3, p<0.01). At the nadir of EAN, spleen weight and lymphocyte proliferation were in line with the clinical severity of the disease. Proliferation tests of purified T cells from naive mice stimulated with phytohemagglutinin or interleukin-12 showed isoform-specific differences (WT≈E4>E3≈E2, p<0.01). Macrophages from both naïve and EAN mice produced nitric oxide upon inflammatory stimulation with lipopolysaccharide, interferon-γ, polyinosinic:polycytidylic acid or combinations thereof, in an isoform-dependent manner (WT≈E4>E2>E3, p<0.01). Generalized intervention with 1400W, a specific inducible nitric oxide synthase inhibitor, significantly suppressed the clinical course of EAN in apoE2, E3 and E4 Tg mice and in WT mice. During the recovery stage of disease, the highest expression of CD178 (FasL) on SCs was found in apoE3 Tg mice. Our data support an isoform-dependent effect of apoE on EAN. This might be due to the isoform-specific effects of apoE on functions of T cells, macrophages and SCs, which contribute to the distinct clinical courses of EAN. ApoE3 might not only inhibit the onset and suppress the clinical severity of EAN, but also enhance the termination of immune responses in the PNS. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/21550340/APOE_ε3_attenuates_experimental_autoimmune_neuritis_by_modulating_T_cell_macrophage_and_Schwann_cell_functions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(11)00147-6 DB - PRIME DP - Unbound Medicine ER -