Intracellular Signal Cascade in CD4⁺ T-Lymphocyte Migration Stimulated by Interferon-gamma-Inducible Protein-10

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N. B. Kukhtina^*, T. I. Arefieva, and T. L. Krasnikova

Group of Neurobiology of Cardiovascular Diseases, Institute of Experimental Cardiology, Russian Cardiology Research Center, 3-ya Cherepkovskaya ul. 15a, 121552 Moscow, Russia; fax: (7-095) 415-2962; E-mail: kukhtina@cardio.ru

^* To whom correspondence should be addressed.

Received May 13, 2004

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The intracellular signal cascades involved in chemokine-stimulated migration of in vitro activated human peripheral blood CD4⁺ T-lymphocytes were investigated. IP-10-mediated chemotactic response of lymphocytes was decreased in the presence of selective inhibitors of Src-kinases (by 40-45%), PI3-kinases (35-40%), and MAP-kinases ERK1/2 (35-40%) and p38 (20%). Combined addition of specific inhibitors of Src-kinases and PI3-kinases and inhibitors of Src-kinases and ERK1/2 MAP-kinases did not result in the further increase of the inhibitory effect, while the combined addition of specific inhibitors of PI3-kinases and ERK1/2 MAP-kinases decreased migration of CD4⁺ T-lymphocytes more effectively (by 55-60%) than any individual inhibitor. Immunoblotting analysis of activation of MAP-kinases ERK1/2 and p38 revealed increased level of phosphorylation of ERK1/2 and p38 MAP-kinases in the presence IP-10. Selective inhibitors of Src-kinases and PI3-kinases significantly inhibited phosphorylation of p38 but did not influence phosphorylation of ERK1/2 MAP-kinases. Our results suggest that Src-kinases, PI3-kinases, and ERK1/2 MAP-kinases are involved in intracellular signal cascade activated during IP-10-stimulated migration of T-lymphocytes, whereas p38 MAP-kinases do not participate in the migration process, although its activation induced by IP-10 depends on Src-kinases and PI3-kinases.

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KEY WORDS: CD4⁺ T-lymphocytes, chemokines, migration, MAP-kinases, PI3-kinases, Src-kinases

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