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PECAM‐1 modulation of immune cell function may play a role in hapten‐induced colitis (trinitrobenzyne sulphonic acid; TNBS)
Author(s) -
Sugimoto Naohito,
Rui Tao,
Stetsenko Inna,
Yoshida Norimasa,
Kvietys Peter R.
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.21.6.a1320
Subject(s) - colitis , chemokine , inflammation , immunology , immune system , endothelial stem cell , chemistry , biology , in vitro , biochemistry
PECAM‐1 is an important adhesion molecule implicated in neutrophil (PMN) transendothelial migration. We have previously shown that TNBS‐induced colitis (colonic mucosal inflammation and injury) is diminished in PECAM‐1 deficient (PECAM −/− ) mice. The aim of the present study was to evaluate potential mechanisms by which PECAM‐1 may play a role in TNBS colitis. Two reciprocal PECAM‐1 chimeras were generated: PECAM‐1 −/− bone marrow (BM) transplanted into wild type irradiated recipient mice (KO to WT; PECAM‐1 localized to recipient endothelial, and other parenchymal, cells) and wild type BM transplanted into PECAM‐1 −/− mice (WT to KO; PECAM‐1 localized to BM‐derived cells). The TNBS‐induced colitis was diminished only in the KO to WT mice; indicating that endothelial cell PECAM‐1 did not play an important role in the colitis. Depletion of colonic macrophages (Mϕ) diminished the TNBS‐induced colitis. Colonic lavage fluid from TNBS‐treated mice increased PMN transendothelial migration; an affect also noted with PECAM‐1 −/− endothelial cells, but not with PECAM‐1 −/− PMN. CLF increased nuclear NFκB and production of the chemokine, KC, from Mϕ isolated from wild type mice, but not Mϕ from PECAM‐1 −/− mice. Collectively, PECAM‐1 may play an important role in TNBS‐induced colitis, not via modulation of endothelial cell function, but by modulating PMN and Mϕ function. Sponsored by CIHR MOP 13668 and MGC 12816.