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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.
AuthorsZhe Ji, Zun-Ji Ke, Jian-Guo Geng
JournalImmunology and cell biology (Immunol Cell Biol) Vol. 90 Issue 4 Pg. 388-95 (Apr 2012) ISSN: 1440-1711 [Electronic] England
PMID21647172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • P-Selectin
  • Serum Amyloid P-Component
  • Integrin alpha4
Topics
  • Adoptive Transfer
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental (drug therapy)
  • Inflammation
  • Integrin alpha4 (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • P-Selectin
  • Serum Amyloid P-Component (pharmacology, therapeutic use)
  • T-Lymphocytes (metabolism)

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