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Título
WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1a
Autor
Año del Documento
2005
Editorial
Oxford University Press
Descripción
Producción Científica
Documento Fuente
International Immunology, 2005, vol. 18, n. 2, p. 221-232
Résumé
Homing of lymphocytes to tissues is a biologically important multistep process that involves selectindependent
rolling, integrin-dependent adhesion and chemokine-directed chemotaxis. The actin
cytoskeleton plays a central role in lymphocyte adhesion and motility. Wiskott–Aldrich syndrome
protein (WASP), the product of the gene mutated in Wiskott–Aldrich syndrome, and its partner,
the Wiskott–Aldrich syndrome protein-interacting protein (WIP), play important roles in actin
re-organization in T lymphocytes. We used mice with disruption of the WASP and WIP genes to
examine the role of WASP and WIP in T cell homing. T cell homing to spleen and lymph nodes in vivo
was deficient in WASP / and WIP / mice and severely impaired in WASP / WIP / double knockout
(DKO) mice. Deficiency of WASP, WIP or both did not interfere with selectin-dependent rolling or
integrin-dependent adhesion of T cells in vitro. Chemotaxis to stromal cell-derived factor-1a (SDF-1a)
in vitro was mildly reduced in T cells from WASP / mice. In contrast, it was significantly impaired in
T cells from WIP / mice and severely reduced in T cells from DKO mice. Cellular F-actin increase
following SDF-1a stimulation was normal in WASP / and WIP / T cells, but severely reduced in
T cells from DKO mice. Actin re-organization and polarization in response to SDF-1a was abnormal in
T cells from all knockout mice. Early biochemical events following SDF-1a stimulation that are
important for chemotaxis and that included phosphorylation of Lck, cofilin, PAK1 and extracellular
regulated kinase (Erk) and GTP loading of Rac-1 were examined in T cells from DKO mice and found to
be normal. These results suggest that WASP and WIP are not essential for T lymphocyte rolling and
adhesion, but play important and partially redundant roles in T cell chemotaxis in vitro and homing
in vivo and function downstream of small GTPases.
Materias (normalizadas)
Biología celular
ISSN
0953-8178
Revisión por pares
SI
Version del Editor
Idioma
eng
Derechos
openAccess
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