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DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration
- Source :
- Blood. 108(7)
- Publication Year :
- 2006
-
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.
- Subjects :
- Chemokine
Lymphocyte
T-Lymphocytes
Immunology
Integrin
Motility
Mice, Transgenic
Ligands
Biochemistry
Mice
Cell Movement
medicine
Animals
Guanine Nucleotide Exchange Factors
Lymphocytes
Lymphocyte homing receptor
biology
Chemokine CCL21
Dock2
GTPase-Activating Proteins
Actin remodeling
Endothelial Cells
Cell Biology
Hematology
Actins
Cell biology
Extracellular Matrix
Mice, Inbred C57BL
medicine.anatomical_structure
Chemokines, CC
biology.protein
Lamellipodium
Chemokines
Subjects
Details
- ISSN :
- 00064971
- Volume :
- 108
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....011dc9b3b0be870c946ba26574132ab3