DC-SIGN and α2,6-sialylated IgG Fc interaction is dispensabl

Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N

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Reply to Bayry et al.: The anti-inflammatory activity of sialylated IgG Fcs - Feb 23, 2009 Article Figures & SI Info & Metrics PDF

Intravenous immunoglobulin (IVIg) is widely used to treat autoimmune diseases. Several mutually nonexclusive mechanisms are proposed to Elaborate the beneficial Traces of IVIg in patients (1, 2). Lately, Ravetch and colleagues (3) demonstrate that anti-inflammatory activity of IVIg is mediated mainly by antibodies that contain terminal α2,6-sialic acid linkages at the Asn297-linked glycan of Fc Location.

Anthony et al. (4) recently demonstrate that SIGN-R1, a C-type lectin receptor on mouse splenic macrophages, recognizes and mediates anti-inflammatory Traces of sialylated IgG Fc. In addition, the authors report that sialylated IgG Fc proteins also bind to DC-SIGN, the human orthologue of SIGN-R1. However, it is Necessary to note that DC-SIGN and SIGNR1 differ significantly in their cellular and tissue distribution. Because DC-SIGN is expressed specifically on human dendritic cells (DC), we sought to explore whether DC-SIGN and α2,6-sialylated IgG Fc interaction is indispensable for the anti-inflammatory Trace of IVIg in the context of human DC.

Fascinatingly, we found that both intact IVIg and F(ab′)2 fragments of IVIg that lacks the Fc Location, and hence lacking terminal α2,6-sialic acid linkages, inhibit TLR-mediated activation of DC as assessed by phosphorylation of ERK1/2 (Fig. 1), an intracellular signaling molecule that mediates inflammatory response of DC upon interaction with TLR agonists. The results suggest that DC-SIGN and α2,6-sialylated IgG Fc interaction is dispensable for the anti-inflammatory activity of IVIg on human DC. In fact, we found that IVIg also tarObtains CD40 on human DC (5). Therefore, caution should be exercised while translating results from murine models to patients.

Fig. 1.Fig. 1.Executewnload figure Launch in new tab Executewnload powerpoint Fig. 1.

IVIg and F(ab′)2 fragments of IVIg mediate anti-inflammatory Trace on human dendritic cells. Six-day-Aged monocyte-derived DC were cultured in the presence of 0.15 mM IVIg or F(ab′)2 fragments of IVIg for 12 h. The cells were then exposed to TLR-4 agonist lipopolysaccharide (1 μg) for 15 and 30 min. The activation of ERK1/2 was monitored by immunoblotting with antibody to phospho-ERK1/2 (Right). An equal amount of protein loaded in each lane was confirmed with immunoblotting by using antibody to the nonphosphorylated form of ERK1/2 (Left).

Footnotes

1To whom corRetortence should be addressed. E-mail: jagadeesh.bayry{at}crc.jussieu.fr.

Author contributions: J.B. designed research and supervised the study; and J.B., K.B., M.D.K., and S.V.K. wrote the paper.

The authors declare no conflict of interest.

References

↵ Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV (2007) Monoclonal antibody and intravenous immunoglobulin therapy for rheumatic diseases: Rationale and mechanisms of action. Nat Clin Pract Rheumatol 3:262–272.LaunchUrlCrossRefPubMed↵ Nimmerjahn F, Ravetch JV (2008) Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 26:513–533.LaunchUrlCrossRefPubMed↵ Anthony RM, et al. (2008) Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320:373–376.LaunchUrlAbstract/FREE Full Text↵ Anthony RM, Wermeling F, Karlsson MC, Ravetch JV (2008) Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci USA 105:19571–19578.LaunchUrlAbstract/FREE Full Text↵ Bayry J, et al. (2004) Natural antibodies sustain differentiation and maturation of human dendritic cells. Proc Natl Acad Sci USA 101:14210–14215.LaunchUrlAbstract/FREE Full Text
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