title: SAP suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) T cell-mediated disease of the central nervous system. Serum amyloid P component (SAP) is a highly conserved plasma protein named for its universal presence in amyloid deposits. Here we report that SAP-transgenic mice had unexpectedly attenuated EAE due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35-55 in complete Freund's adjuvant, SAP-transgenic mice showed reduced spinal cord inflammation with lower severity of EAE attacks as compared with control C57BL/6 mice. However, in SAP-Knockout mice, the severity of EAE is enhanced. Adoptive transfer of Ag-restimulated T cells from wild type to SAP-transgenic mice, or transfer of SAP-transgenic Ag-restimulated T cells to control mice, induced milder EAE. T cells from MOG-primed SAP-transgenic mice showed weak proliferative responses. Furthermore, in SAP-transgenic mice, there is little infiltration of CD45-positive cells in the spinal cord. In vitro, SAP suppressed the secretion of interleukin-2 stimulated by P-selectin and blocked P-selectin binding to T cells. Moreover, SAP could change the affinity between α4-integrin and T cells. These data suggested that SAP could antagonize the development of the acute phase of inflammation accompanying EAE by modulating the function of P-selectin.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. jizhe2008@gmail.com
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ji
authors.forename: Zun-Ji
authors.initials: ZJ
authors.lastname: Ke
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Geng
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D007249:Inflammation; D039441:Integrin alpha4 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019007:P-Selectin; D000683:Serum Amyloid P-Component / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D019007:P-Selectin; D000683:Serum Amyloid P-Component; D039441:Integrin alpha4