title: Endogenous PMN sialidase activity exposes activation epitope on CD11b/CD18 which enhances its binding interaction with ICAM-1.
abstract: Diapedesis is a dynamic, highly regulated process by which leukocytes are recruited to inflammatory sites. We reported previously that removal of sialyl residues from PMNs enables these cells to become more adherent to EC monolayers and that sialidase activity within intracellular compartments of resting PMNs translocates to the plasma membrane following activation. We did not identify which surface adhesion molecules were targeted by endogenous sialidase. Upon activation, β2 integrin (CD11b/CD18) on the PMN surface undergoes conformational change, which allows it to bind more tightly to the ICAM-1 and ICAM-2 on the EC surface. Removal of sialyl residues from CD18 and CD11b, by exogenous neuraminidase or mobilization of PMN sialidase, unmasked activation epitopes, as detected by flow cytometry and enhanced binding to ICAM-1. One sialidase isoform, Neu1, colocalized with CD18 on confocal microscopy. Using an autoperfused microflow chamber, desialylation of immobilized ICAM-1 enhanced leukocyte arrest in vivo. Further, treatment with a sialidase inhibitor in vivo reversed endotoxin-induced binding of leukocytes to ICAM-1, thereby suggesting a role for leukocyte sialidase in the cellular arrest. These data suggest that PMN sialidase could be a physiologic source of the enzymatic activity that removes sialyl residues on β2 integrin and ICAM-1, resulting in their enhanced interaction. Thus, PMN sialidase may be an important regulator of the recruitment of these cells to inflamed sites.
authors.affiliation: Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Chiguang
authors.initials: C
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Lama
authors.initials: L
authors.lastname: Almulki
authors.forename: Sepideh
authors.initials: S
authors.lastname: Faez
authors.forename: Melissa
authors.initials: M
authors.lastname: Whitford
authors.forename: Ali
authors.initials: A
authors.lastname: Hafezi-Moghadam
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cross
mesh_terms: D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism*; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D000939:Epitopes / Q000378:metabolism*; D006801:Humans; D039641:Integrin beta Chains; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D011485:Protein Binding
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D000939:Epitopes; C509295:ITGAM protein, human; D039641:Integrin beta Chains; D018799:Intercellular Adhesion Molecule-1; C486385:NEU1 protein, human; D009439:Neuraminidase