DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration

Ziv Shulman, Ronit Pasvolsky, Eilon Woolf, Valentin Grabovsky, Sara W. Feigelson, Noam Erez, Yoshinori Fukui, Ronen Alon

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

Rac GTPases are key regulators of leukocyte motility. In lymphocytes, chemokine-mediated Rac activation depends on the CDM adaptor DOCK2. The present studies addressed the role of DOCK2 in chemokine-triggered lymphocyte adhesion and motility. Rapid chemokine-triggered activation of both LFA-1 and VLA-4 integrins took place normally in DOCK2-/- T lymphocytes under various shear flow conditions. Consequently, DOCK2-/- T cells arrested normally on TNFα-activated endothelial cells in response to integrin stimulatory chemokine signals, and their resistance to detachment was similar to that of wild-type (wt) T lymphocytes. Nevertheless, DOCK2-/- T lymphocytes exhibited reduced microvillar collapse and lamellipodium extension in response to chemokine signals, ruling out a role for these events in integrin-mediated adhesion strengthening. Strikingly, arrested DOCK2 -/- lymphocytes transmigrated through a CCL21-presenting endothelial barrier with similar efficiency and rate as wt lymphocytes but, unlike wt lymphocytes, could not locomote away from the transmigration site of the basal endothelial side. DOCK2-/- lymphocytes also failed to laterally migrate over multiple integrin ligands coimmobilized with chemokines. This is a first indication that T lymphocytes use 2 different chemokine-triggered actin remodeling programs: the first, DOCK2 dependent, to locomote laterally along apical and basal endothelial surfaces; the second, DOCK2 independent, to cross through a chemokine-bearing endothelial barrier.

Original languageEnglish
Pages (from-to)2150-2158
Number of pages9
JournalBlood
Volume108
Issue number7
DOIs
Publication statusPublished - Oct 1 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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