Experimental allergic encephalomyelitis is inhibited in transgenic mice expressing human C-reactive protein

被引:74
作者
Szalai, AJ [1 ]
Nataf, S
Hu, XZ
Barnum, SR
机构
[1] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA
关键词
D O I
10.4049/jimmunol.168.11.5792
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We show here using a transgenic model that human C-reactive protein (CRP) protects against experimental allergic encephalomyelitis (EAE) in C57BL/6 mice. In transgenic compared with wild-type females, the duration of the human CRP acute phase response that accompanies the inductive phase of active EAE correlates with a delay in disease onset. In transgenic males, which have higher human CRP expression than females do, EAE is delayed, and its severity is reduced relative to same-sex controls. Furthermore, in male transgenics, there is little or no infiltration of the spinal cord by CD3(+) T cells and CD11b(+) monocytes and macrophages, and EAE is sometimes prevented altogether. CRP transgenics also resist EAE induced passively by transfer of encephalitogenic T cells from wild-type donors. Human CRP has three effects on cultured encephalitogenic cells that could contribute to the protective effect observed in vivo: 1) CRP inhibits encephalitogenic peptide-induced proliferation of T cells; 2) CRP inhibits production of inflammatory cytokines (TNF-alpha, IFN-gamma) and chemokines (macrophage-inflammatory protein-la, RANTES, monocyte chemoattractant protein-1); and 3) CRP increases IL-10 production. All three of these actions are realized in vitro only in the presence of high concentrations of human CRP. The combined data suggest that during the acute phase of inflammation accompanying EAE, the high level of circulating human CRP that is achieved in CRP-transgenic mice inhibits the damaging action of inflammatory cells and/or T cells that otherwise support onset and development of EAE.
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页码:5792 / 5797
页数:6
相关论文
共 50 条
[21]  
Karpus WJ, 1998, J IMMUNOL, V161, P2667
[22]  
Kassiotis G, 1999, EUR J IMMUNOL, V29, P774, DOI 10.1002/(SICI)1521-4141(199903)29:03<774::AID-IMMU774>3.3.CO
[23]  
2-K
[24]   DEMONSTRATION OF CALCIUM-INDUCED CONFORMATIONAL CHANGE(S) IN C-REACTIVE PROTEIN BY USING MONOCLONAL-ANTIBODIES [J].
KILPATRICK, JM ;
KEARNEY, JF ;
VOLANAKIS, JE .
MOLECULAR IMMUNOLOGY, 1982, 19 (09) :1159-1165
[25]   Induction and suppression of collagen-induced arthritis is dependent on distinct Fcγ receptors [J].
Kleinau, S ;
Martinsson, P ;
Heyman, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (09) :1611-1616
[26]   Tumour necrosis factor-α and interferon-γ synergistically activate the RANTES promoter through nuclear factor κB and interferon regulatory factor 1 (IRF-1) transcription factors [J].
Lee, AH ;
Hong, JH ;
Seo, YS .
BIOCHEMICAL JOURNAL, 2000, 350 :131-138
[27]  
MARNELL LL, 1995, J IMMUNOL, V155, P2185
[28]   Regulation of complement activation by C-reactive protein [J].
Mold, C ;
Gewurz, H ;
Du Clos, TW .
IMMUNOPHARMACOLOGY, 1999, 42 (1-3) :23-30
[29]   EFFECTS OF C-REACTIVE PROTEIN ON LYMPHOCYTE FUNCTIONS .3. INHIBITION OF ANTIGEN-INDUCED LYMPHOCYTE STIMULATION AND LYMPHOKINE PRODUCTION [J].
MORTENSEN, RF ;
BRAUN, D ;
GEWURZ, H .
CELLULAR IMMUNOLOGY, 1977, 28 (01) :59-68
[30]  
Mossman T.R., 1991, IMMUNOL TODAY, V12-7, pA49