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Fut3‐driven expression of Sialyl Lewis A on intestinal epithelium regulates PMN clearance
Author(s) -
Brazil Jennifer,
Liu R,
Cummings R. D,
Parkos C. A,
Louis N. A
Publication year - 2013
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.27.1_supplement.137.7
Subject(s) - glycan , sialyl lewis x , epitope , glycocalyx , biology , microbiology and biotechnology , immunology , epithelium , immune system , inflammation , intestinal mucosa , chemistry , selectin , antigen , glycoprotein , medicine , genetics
Sialic acids are common in vertebrate surface glycans where they contribute to markers of self, regulating host immune responses. Pathogen‐triggered neutrophil (PMN) recruitment is critical for innate immunity, but aberrant PMN accumulation within intestinal crypts marks disease severity in inflammatory bowel disease (IBD). Using a novel mAb GM35, we identified the tetrasaccharide epitope, sialyl Lewis a (sLe a ) as the terminal structure in an inflammation‐dependent O‐glycan presented on intestinal epithelial cells (IECs). sLe a displayed by CD44v6 regulates PMN transepithelial migration (TEM) through limiting CD44v6 cleavage. Both sLe a and CD44v6 are expressed only in inflamed mucosa. Immunoblotting and mass spectrometric analyses of human IECs also revealed cell‐specific differences in the presentation of other glycoepitopes. IEC lines with differing sLe a expression were employed to investigate mechanisms governing its synthesis. Real time PCR screening of glycosylating enzymes identified α3/4 fucosyltransferase3 (Fut3) as a candidate regulator of these cell‐specific differences. Thus, we have characterized novel differences in the O‐ and N‐glycan expression of specific glycoepitopes and further demonstrated Fut3‐driven expression of sLe a as an important mechanism regulating PMN TEM in inflamed intestine. Pharmacologic targeting of glycan expression may lead to novel therapies for IBD.