Journal of Neuroimmunology
Volume 221, Issue 1 , Pages 46-52, 15 April 2010

Inhibition of C5a receptor alleviates experimental CNS lupus

  • Alexander Jacob

      Affiliations

    • Department of Medicine, University of Chicago, Chicago, IL 60637, United States
    • ,
  • Bradley Hack

      Affiliations

    • Department of Medicine, University of Chicago, Chicago, IL 60637, United States
    • ,
  • Tao Bai

      Affiliations

    • Department of Neurology, University of Chicago, Chicago, IL 60637, United States
    • ,
  • James R. Brorson

      Affiliations

    • Department of Neurology, University of Chicago, Chicago, IL 60637, United States
    • ,
  • Richard J. Quigg

      Affiliations

    • Department of Medicine, University of Chicago, Chicago, IL 60637, United States
    • ,
  • Jessy J. Alexander

      Affiliations

    • Department of Medicine, University of Chicago, Chicago, IL 60637, United States
    • Corresponding Author InformationCorresponding author. Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC5100, Chicago, IL 60637, United States.

Received 10 December 2009; received in revised form 11 February 2010; accepted 11 February 2010. published online 08 March 2010.

Abstract 

To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF-α and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK, pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/lpr brains. MRL/lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus.

Abbreviations: SLE, System lupus erythematosus, IC, Immune complex, qRT-PCR, Quantitative RT-PCR, C5aRant, Antagonist of C5aR, PKB, Protein kinase B, CNS, Central nervous system, MAC, Membrane attack complex, Crry, CR1-related protein y, CSF, Cerebrospinal fluid, MRL/lpr, MRL/MpJ-Tnfrsf6lpr/lpr, MRL+/+, MRL/MpJ-Tnfrsf6+/+, ERK, Extracellular signal-regulated kinase, JNK, c-Jun N-terminal kinase

Keywords: Inflammation, Complement system, Anaphylatoxins, Brain, Systemic lupus erythematosus

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PII: S0165-5728(10)00060-3

doi:10.1016/j.jneuroim.2010.02.011

Journal of Neuroimmunology
Volume 221, Issue 1 , Pages 46-52, 15 April 2010

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