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More MS news articles for November 2002

Chemokine-independent preference of T-helper-1 Cells in transendothelial migration

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J Biol Chem 2002 Oct 20
Katakai T, Hara T, Sugai M, Gonda H, Nambu Y, Matsuda E, Agata Y, Shimizu A.
Center for Molecular Biology and Genetics, Kyoto University, Kyoto, Kyoto 606-8507.

We analyzed differences in the transendothelial migration (TEM) ability between T-helper (Th)-1 and Th2 cells across a murine endothelial cell line, F-2, in a static condition.

The TEM abilities of Th1 cells from mice bearing autoimmune diseases and antigen specific Th1 cell lines were several folds higher than those of Th2 cells and lines of the same origin.

These preferences were observed without exogenous chemoattractant and were insensitive to pertussis toxin which completely blocks the TEM induced by exogenous chemoattactants.

Antibodies against LFA-1 and ICAM-1 as well as CD44 markedly blocked TEM of Th1 cells.

TEM ability was also blocked by pharmacological inhibitors for Src-family protein tyrosine kinases (PP2 and herbimycin A), phosphatidylinositol 3-kininase (wortmannin), and phosphatidylinositol-specific phospholipase C (U73122).

Cross-linking of CD44 strongly induced highly elongated morphology in Th1 lines but weakly in Th2 lines.

The pharmacological inhibitors that blocked TEM also inhibited this morphological change whereas pertussis toxin did not.

These data indicate that there are signaling pathways for TEM independent of chemokine attraction but through adhesion molecules including CD44 and that preferences in TEM ability of Th1 over Th2 is formed, at least in part, by intrinsic differences in these pathways.