Contribution of selectin ligands to eosinophil recruitment into the skin of patients with atopic dermatitis.
Leukocyte extravasation is initiated by interaction with endothelial selectins through selectin ligands. To understand the relative roles of E- and P-selectin in eosinophil recruitment in inflamed skin, we examined the expression of sialyl-Lewis x (sLex) structures and selectin ligands on eosinophils from patients with atopic dermatitis using whole blood flow cytometry. None of the eosinophils from the blood of patients expressed HECA452 (a lymphocyte receptor for skin homing) or CSLEX1 epitopes, and they had little avidity for soluble E-selectin. Whereas levels of the FH6 epitope (sialyl-dimeric Lex) varied on blood eosinophils, none of the infiltrative eosinophils in the skin lesions of patients expressed any type of sLex structures on the surface. In contrast, blood eosinophils bound to soluble P-selectin. The amount of P-selectin that bound to eosinophils was significantly greater in patients with atopic dermatitis than in healthy donors. PSGL-1 expression between these two groups did not differ. Furthermore, eosinophils expressed a large amount of alpha (1, 3) fucosyltransferase (FucT)-IV mRNA, but remarkably little or no FucT-VII mRNA compared with neutrophils. These data indicate that eosinophil interaction with endothelial P-selectin is far more important than interaction with E-selectin for recruitment into the inflamed skin of patients with atopic dermatitis. None of HECA452, 2H5, CSLEX1 or FH6 antigens functioned as a specific receptor to promote preferential skin infiltration via adhesion to endothelial E-selectin. FucT-IV in eosinophils may be more relavent to the generation of functional P-selectin ligand than FucT-VII.
Satoh
Takahiro
T
Department of Dermatology and Immunodermatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. tasa-1688.derm@tmd.ac.jp
Kaneko
Michiyo
M
Wu
Ming-Hua
MH
Yokozeki
Hiroo
H
Nishioka
Kiyoshi
K
D000328:Adult; D016022:Case-Control Studies; D002465:Cell Movement; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019040:E-Selectin / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009844:Oligosaccharides / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D012867:Skin / Q000276:immunology / Q000473:pathology
D019040:E-Selectin; D008024:Ligands; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D019007:P-Selectin; C084882:P-selectin ligand protein; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase