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 Google Scholar Articles by Ali, S. Articles by Kirby, J. A. PubMed PubMed Citation Articles by Ali, S. Articles by Kirby, J. A.

Leukocyte Extravasation: An Immunoregulatory Role for -L-Fucosidase?¹

Simi Ali^2,*, Yvonne Jenkins^*, Maureen Kirkley^*, Athanasios Dagkalis, Ayyakkannu Manivannan, Isabel Joan Crane and John A. Kirby^*

^* Applied Immunobiology and Transplantation Group, Institute of Cellular Medicine, Medical School, University of Newcastle Upon Tyne, Newcastle Upon Tyne, United Kingdom; and Department of Ophthalmology, University of Aberdeen, Institute of Medical Sciences, Forresterhill, Aberdeen, United Kingdom

Fucosylated oligosaccharides and glycoconjugates have been implicated in several biological events, including the cell-cell adhesion processes that mediate inflammation. -L-Fucosidase (ALF) is an exoglycosidase that is involved in the hydrolytic degradation of -L-fucose from glycoconjugates. In this study, we investigated the potential role of ALF in regulation of leukocyte migration. Measurement of transendothelial migration in response to CCL5 demonstrated that pretreatment of monocytic cells with ALF reduced migration (p = 0.0004) to a greater extent than treatment of the endothelial monolayer (p = 0.0374). Treatment with ALF significantly reduced the adhesion of monocytic cells to immobilized P-selectin.Fc. A murine model of experimental autoimmune uveitis was then used to show that treatment of splenic cells with ALF produced an 8.6-fold decrease in rolling and a 3.2-fold decrease in cell migration across the retinal vasculature. Further in vitro studies demonstrated that treatment of monocytes with the chemokines CCL3 or CCL5 increased the level of mRNA encoding ALF; this was accompanied by the detection of significant increases in both the 51- and 56-kDa components of ALF by Western blotting. Treatment of monocytic cells with ALF for 2 h significantly reduced the cell surface expression of CD31, with a further decrease in expression observed after 5 h (p = 0.002). Thus, CD31 and fucosylated ligands of P-selectin seem to be the candidates through which ALF mediates its effect in vitro. These data identify a previously unrecognized immunoregulatory role for ALF in late stages of inflammation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Northern Counties Kidney Research Fund and the Wellcome Trust-078892.

² Address correspondence and reprint requests to Dr. Simi Ali, University of Newcastle upon Tyne, The Medical School, Newcastle upon Tyne, NE2 4HH United Kingdom. E-mail address: simi.ali{at}newcastle.ac.uk

³ Abbreviations used in this paper: ALF, -L-fucosidase; EAU, experimental autoimmune uveoretinitis; PSGL-1, P-selectin glycoprotein ligand-1; SLO, scanning laser ophthalmoscopy.