Leukocyte extravasation: An immunoregulatory role for alpha-L-Fucosidase?

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2407-2413
Number of pages7
JournalThe Journal of Immunology
Volume181
Issue number4
Publication statusPublished - 15 Aug 2008

Keywords

  • E-selectin
  • migration
  • adhesion
  • PECAM-1
  • retina
  • cells
  • mice
  • recruitment
  • fucoidin
  • passage

Cite this

Ali, S., Jenkins, Y., Kirkley, M., Dagkalis, A., Manivannan, A., Crane, I. J., & Kirby, J. A. (2008). Leukocyte extravasation: An immunoregulatory role for alpha-L-Fucosidase? The Journal of Immunology, 181(4), 2407-2413.

Leukocyte extravasation : An immunoregulatory role for alpha-L-Fucosidase? / Ali, Simi; Jenkins, Yvonne; Kirkley, Maureen; Dagkalis, Athanasios; Manivannan, Ayyakkannu; Crane, Isabel Joan; Kirby, John A.

In: The Journal of Immunology, Vol. 181, No. 4, 15.08.2008, p. 2407-2413.

Research output: Contribution to journalArticle

Ali, S, Jenkins, Y, Kirkley, M, Dagkalis, A, Manivannan, A, Crane, IJ & Kirby, JA 2008, 'Leukocyte extravasation: An immunoregulatory role for alpha-L-Fucosidase?', The Journal of Immunology, vol. 181, no. 4, pp. 2407-2413.
Ali S, Jenkins Y, Kirkley M, Dagkalis A, Manivannan A, Crane IJ et al. Leukocyte extravasation: An immunoregulatory role for alpha-L-Fucosidase? The Journal of Immunology. 2008 Aug 15;181(4):2407-2413.
Ali, Simi ; Jenkins, Yvonne ; Kirkley, Maureen ; Dagkalis, Athanasios ; Manivannan, Ayyakkannu ; Crane, Isabel Joan ; Kirby, John A. / Leukocyte extravasation : An immunoregulatory role for alpha-L-Fucosidase?. In: The Journal of Immunology. 2008 ; Vol. 181, No. 4. pp. 2407-2413.
@article{7735b95d72ba42c9890203d44809ecf4,
title = "Leukocyte extravasation: An immunoregulatory role for alpha-L-Fucosidase?",
abstract = "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.",
keywords = "E-selectin, migration, adhesion, PECAM-1, retina, cells, mice, recruitment, fucoidin, passage",
author = "Simi Ali and Yvonne Jenkins and Maureen Kirkley and Athanasios Dagkalis and Ayyakkannu Manivannan and Crane, {Isabel Joan} and Kirby, {John A.}",
year = "2008",
month = "8",
day = "15",
language = "English",
volume = "181",
pages = "2407--2413",
journal = "The Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Leukocyte extravasation

T2 - An immunoregulatory role for alpha-L-Fucosidase?

AU - Ali, Simi

AU - Jenkins, Yvonne

AU - Kirkley, Maureen

AU - Dagkalis, Athanasios

AU - Manivannan, Ayyakkannu

AU - Crane, Isabel Joan

AU - Kirby, John A.

PY - 2008/8/15

Y1 - 2008/8/15

N2 - 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.

AB - 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.

KW - E-selectin

KW - migration

KW - adhesion

KW - PECAM-1

KW - retina

KW - cells

KW - mice

KW - recruitment

KW - fucoidin

KW - passage

M3 - Article

VL - 181

SP - 2407

EP - 2413

JO - The Journal of Immunology

JF - The Journal of Immunology

SN - 0022-1767

IS - 4

ER -