T cell independent mechanism for copolymer‐1‐induced neuroprotection

European Journal of Immunology - Tập 37 Số 11 - Trang 3143-3154 - 2007
Jianuo Liu1,2,3, Thomas V. Johnson2,3,4, Jamie S. Lin1,2,3, Servio H. Ramirez1,2,5, Tatiana K. Bronich6, Steve Caplan7, Yuri Persidsky1,2,5, Howard E. Gendelman1,2, Jonathan Kipnis1,8,2,3,4
1Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska, USA
2Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA
3Laboratory of Neuro-Immune Regulation, University of Nebraska Medical Center, Omaha, Nebraska, USA
4Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA
5Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
6Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA
7Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
8Department of Neuroscience, University of Virginia, Charlottesville, Virginia, USA

Tóm tắt

AbstractDespite active investigation of copolymer‐1 (Cop‐1) for nearly 40 years the mechanisms underlying its neuroprotective properties remain contentious. Nonetheless, current dogma for Cop‐1 neuroprotective activities in autoimmune and neurodegenerative diseases include bystander suppression of autoimmune T cells and attenuation of microglial responses. In this report, we demonstrate that Cop‐1 interacts directly with primary human neurons and decreases neuronal cell death induced by staurosporine or oxidative stress. This neuroprotection is mediated through protein kinase Cα and brain‐derived neurotrophic factor. Dendritic cells (DC) uptake Cop‐1, deliver it to the injury site, and release it in an active form. Interactions between Cop‐1 and DC enhance DC blood brain barrier migration. In a rat model with optic nerve crush injury, Cop‐1‐primed DC induce T cell independent neuroprotection. These findings may facilitate the development of neuroprotective approaches using DC‐mediated Cop‐1 delivery to diseased nervous tissue.

Từ khóa


Tài liệu tham khảo

10.1016/S0764-4469(00)87189-9

10.1385/ABAB:83:1-3:63

Arnon R., 1989, Suppression of experimental allergic encephalomyelitis by COP1‐‐relevance to multiple sclerosis., Isr. J. Med. Sci., 25, 686

10.1073/pnas.2336171100

10.1016/0165-2478(96)02506-0

Filippi M., 2001, Glatiramer acetate reduces the proportion of new MS lesions evolving into “black holes”., Neurology, 57, 731, 10.1212/WNL.57.4.731

10.1517/14656566.2.7.1149

Teitelbaum D., 1997, Copolymer 1 from the laboratory to FDA., Isr. J. Med. Sci., 33, 280

10.1196/annals.1309.055

10.1016/S0165-5728(02)00053-X

10.1073/pnas.97.13.7446

10.1073/pnas.0400569101

10.4049/jimmunol.179.7.4345

10.1016/S1471-4914(02)02373-0

10.1089/089771503767168483

10.1172/JCI23241

10.1073/pnas.041609498

10.1073/pnas.0509438102

10.4049/jimmunol.171.12.6549

10.1111/j.1471-4159.2004.02954.x

10.1007/BF03033818

10.1002/glia.10155

10.1093/toxsci/kfi237

10.1046/j.1471-4159.1999.0720102.x

10.1002/jnr.490360109

10.1016/j.biopsych.2005.06.036

10.1046/j.0022-3042.2001.00752.x

10.1046/j.1471-4159.1997.68020564.x

10.1002/(SICI)1097-0029(19990515/01)45:4/5<276::AID-JEMT11>3.0.CO;2-4

von Bartheld C. S., 1998, Neurotrophins in the developing and regenerating visual system., Histol. Histopathol., 13, 437

10.1016/S0197-0186(96)00071-X

10.1089/neu.1995.12.853

10.1002/(SICI)1097-0029(19991001)47:1<3::AID-JEMT2>3.0.CO;2-2

10.3109/13550289909021287

10.1016/S0002-9440(10)65476-4

10.1002/1521-4141(200207)32:7<2074::AID-IMMU2074>3.0.CO;2-S

10.4049/jimmunol.174.6.3394

10.1006/exnr.1998.6811

10.1007/s11060-004-3339-x

10.1016/j.vaccine.2005.12.056

10.1111/j.0022-202X.2004.23318.x

10.4049/jimmunol.172.10.6281

10.1016/S0165-5728(98)00166-0

10.1073/pnas.96.2.634

10.1038/4734

10.2174/156720105774370258

10.2515/therapie:2005030

10.2174/1568005054201562

10.1523/JNEUROSCI.1859-05.2005

10.1167/iovs.03-0080

10.1007/s00109-005-0689-6

10.1073/pnas.0530191100

10.1111/j.1365-2249.2006.02997.x

10.1191/1352458504ms979oa

10.1016/S1474-4422(05)70167-8

10.1016/j.jneuroim.2003.11.014

Cao M. D., 2003, Modulation effects of human immature and mature dendritic cells on glatiramer acetate specific T cell lines in vitro., Zhongguo Shi Yan Xue Ye Xue Za Zhi, 11, 409

10.1023/A:1015131516649

10.4049/jimmunol.178.1.520

Haugland R. P., 1995, Coupling of monoclonal antibodies with fluorophores., Methods Mol. Biol, 45, 205

10.1189/jlb.0206110

10.1182/blood-2005-11-4721

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European Journal of Immunology

Tập 37 Số 11

3143-3154

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