427회 SIGN-R1 mediated complement activation pathway and its involvemen…

427회 (2009. 6. 11.)

연사:  강 영 선, 건국대학교 의생명과학연구원 의생명과학과

제목:  SIGN-R1 mediated complement activation pathway and its involvement in IVIG effects

Abstract 

The intricate system of serum complement proteins provides resistance to infection. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial binding C3 fragments recognized by leukocytes. The spleen and C3 provide resistance against blood-borne S. pneumoniae infection. To better understand the mechanisms involved, we studied SIGN-R1, a lectin that captures microbial polysaccharides in spleen marginal zone. We found that SIGN-R1 directly bound the complement C1 subcomponent, C1q, and assembled a C3 convertase, but without the traditional requirement for either antibody or factor B. Therefore the transmembrane lectin SIGN-R1 contributes to innate resistance by an unusual C3 activation pathway, unraveling the novel and 4th complement activation pathway. Recently, it has been reported that sialylation on Fc doamin of immunogloublin is critical for the effect of intravenous immunoglobulin (IVIG) and seems to be mediated by lectins which are expressed on splenic marginal zone macrophages (Science 2008. Vol 320. 373., Science 2006. Vol 313. 670). In particular, they observed that the preferential binding of the 2,6- sialylated Fc is distinct on its cognate receptor expressed on a population of macrophages in splenic marginal zone and this binding results in the trans-upregulation of the inhibitory IgG Fc receptor on effector macrophages, located at sites of inflammation (such as the inflamed joint or glomerulus), thus leading to the anti-inflammatory activity of IVIG. Accordingly, it might be suggested that SIGN-R1, a C-type lectin, which is expressed on splenic marginal macrophages, mediate this trans-upregulation of the inhibitory IgG Fc receptor and the anti- inflammatory activity of IVIG. Autoantibody is the principal mediators of autoimmune disease. IVIG is a milestone of the therapy of autoimmune disease. In our further studies, we hope to unravel the specific mechanism of SIGN-R1-mediated IVIG effect and these works could lead to develop a potential therapeutic target against several autoimmune diseases.