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Originally published In Press as doi:10.1074/jbc.M204133200 on October 20, 2002

J. Biol. Chem., Vol. 277, Issue 52, 50948-50958, December 27, 2002
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Chemokine-independent Preference for T-helper-1 Cells in Transendothelial Migration*

Tomoya KatakaiDagger , Takahiro HaraDagger , Manabu SugaiDagger , Hiroyuki GondaDagger , Yukiko NambuDagger , Eishou MatsudaDagger , Yasutoshi AgataDagger , and Akira ShimizuDagger §

From the Dagger  Center for Molecular Biology and Genetics, Kyoto University, and the § Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan

We analyzed differences in the transendothelial migration (TEM) ability of T-helper (Th)-1 and Th2 cells across a murine endothelial cell line (F-2) under static conditions. The TEM abilities of Th1 cells from mice bearing autoimmune diseases and antigen-specific Th1 cell lines were severalfold 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 TEM induced by exogenous chemoattractants. Antibodies against LFA-1 and ICAM-1 as well as CD44 markedly blocked the TEM of Th1 cells. TEM ability was also blocked by pharmacological inhibitors of Src family protein-tyrosine kinases (PP2 and herbimycin A), phosphatidylinositol 3-kinase (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 the preferential TEM ability of Th1 over Th2 cells is formed, at least in part, by intrinsic differences in these pathways.

* This work was supported in part by grants-in-aid from the Ministry of Education, Science, Sports, and Culture of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Center for Molecular Biology and Genetics, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Tel.: 81-75-751-4191; Fax: 81-75-751-4190; E-mail: shimizu@virus.kyoto-u.ac.jp.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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