RhoA activation promotes transendothelial migration of monocytes via ROCK

Henk Honing, Timo K van den Berg, Susanne M A van der Pol, Christine D Dijkstra, Rob A van der Kammen, John G Collard, Helga E de Vries

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88 Citations (Scopus)

Abstract

Monocyte infiltration into inflamed tissue requires the initial arrest of the cells on the endothelium followed by firm adhesion and their subsequent migration. Migration of monocytes and other leukocytes is believed to involve a coordinated remodeling of the actin cytoskeleton. The small GTPases RhoA, Rac1, and Cdc42 are critical regulators of actin reorganization. In this study, we have investigated the role of Rho-like GTPases RhoA, Rac1, and Cdc42 in the adhesion and migration of monocytes across brain endothelial cells by expressing their constitutively active or dominant-negative constructs in NR8383 rat monocytic cells. Monocytes expressing the active form of Cdc42 show a reduced migration, whereas Rac1 expression did not affect adhesion or migration. In contrast, expression of the active form of RhoA in monocytes leads to a dramatic increase in their adhesion and migration across endothelial cells. The effect of RhoA was found to be mediated by its down-stream effector Rho kinase (ROCK), as pretreatment with the selective ROCK inhibitor Y-27632 prevented this enhanced adhesion and migration. These results demonstrate that RhoA activation in monocytes is sufficient to enhance adhesion and migration across monolayers of endothelial cells.

Original languageEnglish
Pages (from-to)523-8
Number of pages6
JournalJournal of leukocyte biology
Volume75
Issue number3
DOIs
Publication statusPublished - Mar 2004

Keywords

  • Actins/metabolism
  • Animals
  • Cell Adhesion
  • Cell Line
  • Chemotaxis, Leukocyte/immunology
  • Cytoskeleton/metabolism
  • Endothelium, Vascular/cytology
  • Inflammation/pathology
  • Intracellular Signaling Peptides and Proteins
  • Microscopy, Video
  • Monocytes/cytology
  • Protein-Serine-Threonine Kinases/physiology
  • Rats
  • cdc42 GTP-Binding Protein/physiology
  • rac1 GTP-Binding Protein/physiology
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein/metabolism

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