HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ellerbroek, P. M. Articles by Coenjaerts, F. E. J. Search for Related Content PubMed PubMed Citation Articles by Ellerbroek, P. M. Articles by Coenjaerts, F. E. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

O-Acetylation of Cryptococcal Capsular Glucuronoxylomannan Is Essential for Interference with Neutrophil Migration¹

Pauline M. Ellerbroek^2,*,, Dirk J. Lefeber^2,*,, Richard van Veghel, Jelle Scharringa^*,, Ellen Brouwer^*,, Gerrit J. Gerwig, Guilhem Janbon^¶, Andy I. M. Hoepelman^*, and Frank E. J. Coenjaerts^3,*,

^* Department of Infectious Diseases and Eijkman Winkler Institute for Microbiology, Division of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands; Department of Bio-Organic Chemistry, Section of Glycoscience and Biocatalysis, Bijvoet Center, Utrecht University, Utrecht, The Netherlands; and ^¶ Unité de Mycologie Moléculaire, Institut Pasteur, Paris, France

The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans has been shown to interfere with neutrophil migration. Although several receptors have been implied to mediate this process, the structural perspectives are unknown. Here, we assess the contribution of 6-O-acetylation and xylose substitution of the (13)--D-mannan backbone of GXM, the variable structural features of GXM, to the interference with neutrophil migration. We compare chemically deacetylated GXM and acetyl- or xylose-deficient GXM from genetically modified strains with wild-type GXM in their ability to inhibit the different phases of neutrophil migration. Additionally, we verify the effects of de-O-acetylation on neutrophil migration in vivo. De-O-acetylation caused a dramatic reduction of the inhibitory capacity of GXM in the in vitro assays for neutrophil chemokinesis, rolling on E-selectin and firm adhesion to endothelium. Genetic removal of xylose only marginally reduced the ability of GXM to reduce firm adhesion. In vivo, chemical deacetylation of GXM significantly reduced its ability to interfere with neutrophil recruitment in a model of myocardial ischemia (65% reduction vs a nonsignificant reduction in tissue myeloperoxidase, respectively). Our findings indicate that 6-O-acetylated mannose of GXM is a crucial motive for the inhibition of neutrophil recruitment.

This article has been cited by other articles:

				P.-Y. Cheng, A. Sham, and J. W. Kronstad Cryptococcus gattii Isolates from the British Columbia Cryptococcosis Outbreak Induce Less Protective Inflammation in a Murine Model of Infection than Cryptococcus neoformans Infect. Immun., October 1, 2009; 77(10): 4284 - 4294. [Abstract] [Full Text] [PDF]

				J. Grijpstra, G. J. Gerwig, H. Wosten, J. P. Kamerling, and H. de Cock Production of Extracellular Polysaccharides by CAP Mutants of Cryptococcus neoformans Eukaryot. Cell, August 1, 2009; 8(8): 1165 - 1173. [Abstract] [Full Text] [PDF]

				G. Rajam, G. M. Carlone, and S. Romero-Steiner Functional Antibodies to the O-Acetylated Pneumococcal Serotype 15B Capsular Polysaccharide Have Low Cross-Reactivities with Serotype 15C Clin. Vaccine Immunol., September 1, 2007; 14(9): 1223 - 1227. [Abstract] [Full Text] [PDF]

				D. C. McFadden, M. De Jesus, and A. Casadevall The Physical Properties of the Capsular Polysaccharides from Cryptococcus neoformans Suggest Features for Capsule Construction J. Biol. Chem., January 27, 2006; 281(4): 1868 - 1875. [Abstract] [Full Text] [PDF]