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Vimentin function in lymphocyte adhesion and transcellular migration.

Mikko Nieminen1, Tiina Henttinen, Marika Merinen

  • 1Turku Centre for Biotechnology, University of Turku and Abo Akademi University, P.O.Box 123, FIN- 20521 Turku, Finland.

Nature Cell Biology
|January 24, 2006
PubMed
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Vimentin intermediate filaments are crucial for lymphocyte transmigration across endothelial cells, facilitating cell adhesion and homing. Deficiencies in vimentin impair leukocyte migration and compromise endothelial barrier function.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Leukocyte adhesion to endothelial cells is understood, but mechanisms of transendothelial migration (diapedesis) are less clear.
  • Leukocytes utilize both paracellular and transcellular routes for migration across the endothelium.

Purpose of the Study:

  • To investigate the role of intermediate filaments, specifically vimentin, in lymphocyte transendothelial migration.
  • To elucidate the mechanisms by which vimentin influences leukocyte adhesion, migration, and homing.

Main Methods:

  • Utilized vimentin-deficient (vim(-/-)) peripheral blood mononuclear cells (PBMCs) and endothelial cells in migration assays.
  • Assessed leukocyte homing to lymphoid organs (mesenteric lymph nodes, spleen) in wild-type and vim(-/-) mice.

Related Experiment Videos

  • Analyzed endothelial integrity and the expression/distribution of key surface molecules (ICAM-1, VCAM-1, integrin-beta1).

    • Main Results:

    • Peripheral blood mononuclear cells (PBMCs) preferentially use the transcellular route for migration.
    • Vimentin-deficient PBMCs and endothelial cells showed significantly reduced initiation of transendothelial migration.
    • Vimentin deficiency impaired PBMC homing to lymphoid organs and compromised endothelial barrier function.
    • Absence of vimentin led to aberrant expression and distribution of adhesion molecules critical for homing.

    Conclusions:

    • Intermediate filaments, particularly vimentin, play an active and essential role in lymphocyte adhesion and transmigration.
    • Vimentin is critical for regulating endothelial barrier function and leukocyte extravasation.
    • Vimentin influences the expression of adhesion molecules necessary for effective leukocyte homing to secondary lymphoid organs.