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Nitric oxide induces polarization of actin in encephalitogenic T cells and inhibits their in vitro transendothelial migration in a p70S6 kinase‐independent manner
Author(s) -
Staykova Maria A.,
Berven Leise A.,
Cowden William B.,
Willenborg David O.,
Crouch Michael F.
Publication year - 2003
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/fj.02-0577fje
Subject(s) - cell migration , microbiology and biotechnology , t cell , in vitro , nitric oxide , inhibitory postsynaptic potential , endothelial stem cell , chemistry , lymphoblast , biology , cell culture , biochemistry , immunology , immune system , endocrinology , genetics , organic chemistry
Nitric oxide (NO) inhibits both actively induced and transferred autoimmune encephalomyelitis. To explore potential mechanisms, we examined the ability of NO to inhibit migration of T lymphoblasts through both collagen matrices and monolayers of rat brain endothelial cells. The NO donor 1‐hydroxy‐2‐oxo‐3, 3‐bis (2‐aminoethyl)‐1‐triazene (HOBAT) inhibited migration in a concentration‐dependent manner. NO pretreatment of T cells inhibited migration through untreated endothelial cells, but NO pretreatment of endothelial cells had no inhibitory effect on untreated T cells. Therefore NO's migration inhibitory action was mediated through its effect on T cells and not endothelial cells. HOBAT did not inhibit migration by inducing T‐cell death but rather by polarizing the T cells, resulting in a morphology suggestive of migrating cells. P70S6 kinase, shown to have a role in NO‐induced migration inhibition in fibroblasts, had no role in the inhibitory effect of NO on T‐cell migration. Thus, HOBAT did not alter p70S6K activity nor did rapamycin, a specific inhibitor of p70S6K, inhibit HOBAT‐induced T‐cell morphological changes or T‐cell migration. We suggest that NO‐induced morphological changes result in T cells with predefined migratory directionality, thus limiting the ability of these cells to respond to other migratory signals.