Vimentin function in lymphocyte adhesion and transcellular migration

Nieminen, Henttinen, Merinen, Marttila-Ichihara, John Eriksson, Jalkanen

    Research output: Contribution to journalArticleScientificpeer-review

    310 Citations (Scopus)

    Abstract

    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-beta1 on PBMCs). These data show that intermediate filaments are active in lymphocyte adhesion and transmigration.
    Original languageUndefined/Unknown
    Pages (from-to)156–162
    JournalNature Cell Biology
    Volume8
    Issue number2
    DOIs
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

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