Abstract:
:The anti-inflammatory activity of intravenous Ig (IVIG) results from a minor population of the pooled IgG molecules that contains terminal alpha2,6-sialic acid linkages on their Fc-linked glycans. These anti-inflammatory properties can be recapitulated with a fully recombinant preparation of appropriately sialylated IgG Fc fragments. We now demonstrate that these sialylated Fcs require a specific C-type lectin, SIGN-R1, (specific ICAM-3 grabbing non-integrin-related 1) expressed on macrophages in the splenic marginal zone. Splenectomy, loss of SIGN-R1(+) cells in the splenic marginal zone, blockade of the carbohydrate recognition domain (CRD) of SIGN-R1, or genetic deletion of SIGN-R1 abrogated the anti-inflammatory activity of IVIG or sialylated Fc fragments. Although SIGN-R1 has not previously been shown to bind to sialylated glycans, we demonstrate that it preferentially binds to 2,6-sialylated Fc compared with similarly sialylated, biantennary glycoproteins, thus suggesting that a specific binding site is created by the sialylation of IgG Fc. A human orthologue of SIGN-R1, DC-SIGN, displays a similar binding specificity to SIGN-R1 but differs in its cellular distribution, potentially accounting for some of the species differences observed in IVIG protection. These studies thus identify an antibody receptor specific for sialylated Fc, and present the initial step that is triggered by IVIG to suppress inflammation.
journal_name
Proc Natl Acad Sci U S Aauthors
Anthony RM,Wermeling F,Karlsson MC,Ravetch JVdoi
10.1073/pnas.0810163105subject
Has Abstractpub_date
2008-12-16 00:00:00pages
19571-8issue
50eissn
0027-8424issn
1091-6490pii
0810163105journal_volume
105pub_type
杂志文章abstract::The origins of the five groups of living seed plants, including the single relictual species Ginkgo biloba, are poorly understood, in large part because of very imperfect knowledge of extinct seed plant diversity. Here we describe well-preserved material from the Early Cretaceous of Mongolia of the previously enigmati...
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pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2003-12-09 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2014-04-22 00:00:00
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pub_type: 杂志文章
doi:10.1073/pnas.92.15.6788
更新日期:1995-07-18 00:00:00