Nitric oxide induces polarization of actin in encephalitogenic T cells and inhibits their in vitro trans-endothelial migration in a p70S6 kinase-independent manner.
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.
Staykova
Maria A
MA
Neurosciences Research Unit, The Canberra Hospital, Australia. maria.staykova@anu.edu.au
Berven
Leise A
LA
Cowden
William B
WB
Willenborg
David O
DO
Crouch
Michael F
MF
D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D000199:Actins / Q000032:analysis*; D000818:Animals; D001921:Brain / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity; D002478:Cells, Cultured; D004285:Dogs; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004727:Endothelium / Q000502:physiology; D008213:Lymphocyte Activation; D018448:Models, Immunological; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D022502:Stress Fibers / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D019108:Tight Junctions / Q000648:ultrastructure; D014226:Triazenes / Q000494:pharmacology
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D000199:Actins; D015815:Cell Adhesion Molecules; D020030:Nitric Oxide Donors; D014226:Triazenes; D009569:Nitric Oxide; D038762:Ribosomal Protein S6 Kinases, 70-kDa