Vimentin function in lymphocyte adhesion and transcellular migration.
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.
Nieminen
Mikko
M
Turku Centre for Biotechnology, University of Turku and Abo Akademi University, P.O.Box 123, FIN- 20521 Turku, Finland.
Henttinen
Tiina
T
Merinen
Marika
M
Marttila-Ichihara
Fumiko
F
Eriksson
John E
JE
Jalkanen
Sirpa
S
D000818:Animals; D002199:Capillary Permeability; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005780:Gelatin / Q000494:pharmacology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008871:Microvilli / Q000502:physiology; D009130:Muscle, Smooth / Q000098:blood supply; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013737:Testis / Q000098:blood supply; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D019012:Integrin beta1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D014746:Vimentin; D018799:Intercellular Adhesion Molecule-1; D007633:Keratins; D005780:Gelatin