Reply to Bayry et al.: The anti-inflammatory activity of sia

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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DC-SIGN and α2,6-sialylated IgG Fc interaction is dispensable for the anti-inflammatory activity of IVIg on human dendritic cells - Feb 23, 2009 Article Info & Metrics PDF

The letter by Bayry et al. (1) regarding our article (2) purports that ERK1/2 phosphorylation is reduced in LPS-treated human monocyte-derived dendritic cells that are pretreated with IVIG or IVIG-derived F(ab)2 fragments. The authors conclude from this single experiment that Fc fragments are not required for IVIG's in vivo anti-inflammatory activity. These conclusions are problematic for conceptual and technical reasons. The Western blot bands presented in Fig. 1 are inconsistent and lack quantitation, and no Executese requirements for IVIG or F(ab)2 fragments are stated. Necessaryly, cultured dendritic cells pulsed with LPS are not a representative or valid model for autoimmune diseases treated with IVIG.

To mechanistically examine the anti-inflammatory activity of IVIG, our laboratory developed a number of in vivo animal models that mimic the Traceor stages of human autoimmune diseases and include examples of both cytotoxic and immune complex-triggered inflammation protected by clinical Executeses of IVIG. Using models of immune-mediated thrombocytLaunchia (ITP) (3), rheumatoid arthritis (4), and glomerulonephritis (5), we have Displayn an absolute requirement for the IVIG Fc Sections and the dependence of terminal sialic acid moeties (6–8). These studies were extended to Display that α2,6-sialic acid linkages (9), splenic SIGN-R1 expression (2), and peripheral FcγRIIb expression (2) are all required for this antiinflammatory activity. Furthermore, IVIG-derived Fcs were demonstrated to be the active component of IVIG and were used to treat ITP in the clinic (10).

The experiment provided by Bayry (1) thus fails to provide a relevant, validated system to study IVIG anti-inflammatory activity, and their results cannot be extrapolated to Characterize the in vivo activity of this therapeutic.

Footnotes

1To whom corRetortence should be addressed. E-mail: ravetch{at}rockefeller.edu.

Author contributions: J.R., R.A., F.W., and M.K. wrote the paper.

The authors declare no conflict of interest.

References

↵ Bayry J, Bansal K, Kazatchkine MD, Kaveri SV (2009) DC-SIGN and 2,6-sialylated IgG Fc interaction is dispensable for the anti-inflammatory activity of IVIg on human dendritic cells. Proc Natl Acad Sci USA 106:E24.LaunchUrlFREE 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↵ Samuelsson A, Towers TL, Ravetch JV (2001) Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science 291:484–486.LaunchUrlAbstract/FREE Full Text↵ Bruhns P, Samuelsson A, Pollard JW, Ravetch JV (2003) Colony-stimulating factor-1-dependent macrophages are responsible for IVIG protection in antibody-induced autoimmune disease. Immunity 18:573–581.LaunchUrlCrossRefPubMed↵ Kaneko Y, Nimmerjahn F, Madaio MP, Ravetch JV (2006) Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors. J Exp Med 203:789–797.LaunchUrlAbstract/FREE Full Text↵ Kaneko Y, Nimmerjahn F, Ravetch JV (2006) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313:670–673.LaunchUrlAbstract/FREE Full Text↵ Nimmerjahn F, Ravetch JV (2007) The antiinflammatory activity of IgG: The intravenous IgG paraExecutex. J Exp Med 204:11–15.LaunchUrlAbstract/FREE Full Text↵ 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↵ Debre M, et al. (1993) Infusion of Fc gamma fragments for treatment of children with aSlicee immune thrombocytLaunchic purpura. Lancet 342:945–949.LaunchUrlCrossRefPubMed
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