Deletion of both ICAM-1 and C3 enhances severity of experimental autoimmune encephalornyelitis compared to C3-deficient mice

NEUROSCIENCE LETTERS

卷:442

Article

Smith, Sherry S.¹  Ludwig, Michael¹  Wohler, Jillian E.¹  Bullard, Daniel C.²  Szalai, Alex J.³  Barnum, Scott R.^1,4 

[1] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA

[2] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA

[3] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[4] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA

关键词: experimental autoimmune;    encephalomyelitis;    adhesion molecules;    complement;    neuroimmunology;   

DOI  :  10.1016/j.neulet.2008.07.005

来源: Elsevier

【 摘 要 】

Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous system (CNS) inflammation and leukocyte infiltration, demyelination of neurons, and blood-brain barrier breakdown. The development of experimental autoimmune encephalomyelitis (EAE), the animal model for MS is dependent on a number of components of the immune system including complement and adhesion molecules. Previous studies in our lab have examined the role of C3, the central complement component, and intercellular adhesion molecule-1 (ICAM-1) a key cell adhesion molecule involved in leukocyte trafficking to sites of inflammation including the CNS. In these studies we demonstrated that myelin oligodendrocyte glycoprotein (MOG)-induced EAE is markedly attenuated in both ICAM-1(-/-) and C3(-/-) mice. Given the pivotal role that these proteins play in EAE, we hypothesized that EAE in ICAM-1(-/-) and C3(-/-) double mutant mice would likely fail to develop. Unexpectedly, EAE in ICAM-1(-/-) x C3-/- mice was only modestly attenuated compared to wild type mice and significantly worse than C3(-/-) mice. Leukocyte infiltration was commensurate with disease severity between the three groups of mice. Spinal cord T cells from ICAM-1(-/-) x C3(-1-) mice produced the highest levels of IFN-gamma and TNF-alpha, despite reduced disease severity compared to wild type mice. The mechanisms behind the elevated EAE severity in ICAM-1(-/-) x C3(-/-) mice may relate to altered homing of leukocytes or processing of self-antigens in the double mutant background. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

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