Vimentin function in lymphocyte adhesion and transcellular migration

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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-β1 on PBMCs). These data show that intermediate filaments are active in lymphocyte adhesion and transmigration.

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Figure 1: Vimentin intermediate filaments are involved in PBMC transcellular migration and in vivo homing.
Figure 2: Leukocyte–endothelial cell interactions, and endothelial integrity are compromised in vim−/− mice.
Figure 3: Reorganization of vimentin and keratin intermediate filaments during PBMC transmigration.
Figure 4: Organization and expression of critical surface adhesion molecules is altered in vim−/− endothelial cells and lymphocytes.

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Acknowledgements

We thank H. Saarrento for technical help and A. Sovikoski–Georgieva for secretarial assistance. Funding from the Academy of Finland, the Finnish Cancer Organizations, the Sigrid Jusélius Foundation, and the Association of the Finnish Life Insurance Companies is gratefully acknowledged.

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Correspondence to John E. Eriksson.

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The authors declare no competing financial interests.

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