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Resolvin E1 promotes mucosal surface clearance of neutrophils: a new paradigm for inflammatory resolution
Author(s) -
Campbell Eric L,
Louis Nancy,
Canny Geraldine,
Arita Makoto,
Serhan Charles N,
Colgan Sean P
Publication year - 2007
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.21.5.a131-c
Subject(s) - microbiology and biotechnology , receptor , chemotaxis , epithelium , inflammation , chemistry , immunology , biology , biochemistry , genetics
Migration of neutrophils (PMN) across epithelia is a pathological hallmark of many mucosal diseases. While lesions at mucosal surfaces are generally self‐limiting, endogenous mechanisms of resolution are incompletely understood. Previous studies showed that resolvins directly act on PMN to attenuate transendothelial migration. Less is known about the influence of resolvins on PMN‐epithelial interactions and whether they act on epithelia. We studied the dynamics of resolvin E1 (RvE1) actions on PMN transepithelial migration. PMN exposure to RvE1 or Chemerin (peptide agonist of RvE receptor, ChemR23) reduced transepithelial migration in a dose‐dependent manner. Conversely, activation of epithelial ChemR23 promoted apical clearance of PMN. A non‐biased screen of known PMN‐ligands expressed on epithelial cells in response to RvE1 revealed selective induction of CD55, an apically expressed anti‐adhesive molecule. CD55 promoter analysis confirmed that both RvE1 and Chemerin activate the CD55 promoter. CD55 neutralizing antibody prevented apical clearance of PMN and attenuated transepithelial migration. Together these findings implicate a “two‐hit” model of inflammatory resolution, whereby activation of the PMN RvE receptor attenuates transmigration and subsequent actions on the epithelium promote CD55‐dependent clearance of PMN from the epithelial surface. Funded by NIH Grant P50‐DE‐016191.