Premium
CD44v6 mediates neutrophil clearance from the apical surface of the intestinal epithelium
Author(s) -
Louis Nancy A.,
Lee Winston Y.,
Lockard Catherine M.,
Parkos Charles A.
Publication year - 2009
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.23.1_supplement.236.2
Subject(s) - epithelium , antigen , antibody , inflammation , immunology , epitope , microbiology and biotechnology , chemistry , biology , pathology , medicine
Neutrophil (PMN) infiltration and accumulation are pathognomonic of multiple inflammatory processes of the bowel, including ulcerative colitis, however, the signals governing PMN clearance remain to be defined. Our goal was to identify inflammation responsive epithelial ligands regulating PMN transepithelial migration and clearance. A panel of antibodies was generated against interferon‐gamma (IFNγ)‐stimulated T84 intestinal epithelial cell membranes. Once such antibody, GM35, recognizes an IFNγ‐responsive antigen and reduces PMN transepithelial migration in a time and dose dependent manner. Immunohistochemical staining and selective surface biotinylation localize the GM35 antigen to the apical surface of T84 cells, and further work indicates that the GM35 epitope is cleaved from T84 cells during PMN transepithelial migration. Antigen immunoprecipitation and confocal microscopic analysis of immunofluorescently labeled T84 cells indicate that GM35 binds a member of the CD44 family, while microsequencing more specifically identifies the GM35 ligand as the CD44 variant CD44v6. These studies identify CD44v6 as a candidate mediator of intestinal epithelial PMN clearance and a potential target 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.