Leukocyte extravasation: an immunoregulatory role for alpha-L-fucosidase?
Fucosylated oligosaccharides and glycoconjugates have been implicated in several biological events, including the cell-cell adhesion processes that mediate inflammation. Alpha-L-fucosidase (ALF) is an exoglycosidase that is involved in the hydrolytic degradation of alpha-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.
Ali
Simi
S
Applied Immunobiology and Transplantation Group, Institute of Cellular Medicine, Medical School, University of Newcastle Upon Tyne, Newcastle Upon Tyne, United Kingdom. simi.ali@newcastle.ac.uk
Jenkins
Yvonne
Y
Kirkley
Maureen
M
Dagkalis
Athanasios
A
Manivannan
Ayyakkannu
A
Crane
Isabel Joan
IJ
Kirby
John A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D042783:Endothelial Cells / Q000201:enzymology / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology*; D036904:Leukocyte Rolling / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D012173:Retinitis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D014605:Uveitis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D005644:alpha-L-Fucosidase / Q000502:physiology*
D007155:Immunologic Factors; D005644:alpha-L-Fucosidase