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O‐Glycosylation sites on CD44v6 modulate PMN transepithelial migration
Author(s) -
Brazil Jennifer Catherine,
Lee Winston,
Parkos Charles A,
Louis Nancy A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.355.1
Subject(s) - glycosylation , cd44 , microbiology and biotechnology , muc1 , glycoprotein , gene silencing , antigen , chemistry , ligand (biochemistry) , receptor , biology , immunology , biochemistry , in vitro , gene
The migration of large numbers of neutrophils (PMN) across the apical epithelial surface is a histopathological hallmark of many mucosal inflammatory diseases. However the precise signals governing this process remain poorly defined. Previous studies from our lab have identified an antibody‐GM35 that binds to an apical epithelial ligand and blocks PMN transepithelial migration. Preliminary data identified the GM35 antigen as a v6 exon‐containing variant form of the glycoprotein CD44. In the current study, immunoblotting and confocal microscopic analysis of protein expression and localization in T84 cells confirmed GM35 binding to CD44v6 and further demonstrated binding of GM35 to apically expressed CD44v6. Gene silencing experiments confirmed the identification of the GM35 antigen as epithelial CD44 and demonstrated for the first time a direct functional effect for CD44 in GM35 function. Further work demonstrates that both GM35 ligand binding and the GM35 mediated decrease in PMN detachment/migration are blocked by specific inhibition of O‐Glycosylation. These studies identify epithelial CD44v6 as an important mediator of PMN clearance and suggest that O‐Glycosylation sites on this protein may serve as potential targets for therapeutic intervention. This work is supported by R01 funding (Parkos), an NIH Career Development Award (Louis) and an Emory University Research Council seed grant.