Nature Cell Biology 8, 156 - 162 (2006)
Published online: 22 January 2006; | doi:10.1038/ncb1355
Vimentin function in lymphocyte adhesion and transcellular migrationMikko Nieminen1, 2, 4, Tiina Henttinen1, 2, 4, Marika Merinen3, Fumiko Marttila–Ichihara3, John E. Eriksson1, 2, 5
& Sirpa Jalkanen3, 51
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, P.O.Box 123, FIN- 20521 Turku, Finland. 2
Department of Biology, University of Turku, Science Building 1, FIN-20014 Turku, Finland. 3
Medicity Research Laboratory and Department of Medical Microbiology, University of Turku and National Public Health Institute, Tykistökatu 6, FIN-20520 Turku, Finland. 4
These authors contributed equally to this work. 5
These principal investigators contributed equally to this work.
Correspondence should be addressed to John E. Eriksson john.eriksson@btk.utu.fi vimentinICAM-1VCAM-1integrin- 1TNF- keratinCD44SGLT1PKC Although the adhesive interactions of leukocytes with endothelial cells are well understood, little is known about the detailed mechanisms underlying the actual migration of leukocytes across the endothelium (diapedesis). Leukocytes have been shown to use both paracellular and transcellular routes for transendothelial migration. Here we show that peripheral blood mononuclear cells (PBMCs; T- and B-lymphocytes) preferentially use the transcellular route. The intermediate filaments of both endothelial cells and lymphocytes formed a highly dynamic anchoring structure at the site of contact between these two cell types. The initiation of this process was markedly reduced in vimentin-deficient (vim-/-) PBMCs and endothelial cells. When compared with wild-type PBMCs, vim-/- PBMCs showed a markedly reduced capacity to home to mesenteric lymph nodes and spleen. Furthermore, endothelial integrity was compromised in vim-/- mice, demonstrating that intermediate filaments also regulate the barrier that governs leukocyte extravasation. Absence of vimentin resulted in highly aberrant expression and distribution of surface molecules critical for homing (ICAM-1 and VCAM-1 on endothelial cells and integrin-1 on PBMCs). These data show that intermediate filaments are active in lymphocyte adhesion and transmigration.
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