RT info:eu-repo/semantics/article
T1 WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1a
A1 Gallego, María Dolores
A1 Fuente García, Miguel Ángel de la
A1 Antón, Inés María
A1 Snapper, Scott B.
A1 Fuhlbrigge, Robert
A1 Geha, Raif S.
K1 Biología celular
AB Homing of lymphocytes to tissues is a biologically important multistep process that involves selectindependentrolling, integrin-dependent adhesion and chemokine-directed chemotaxis. The actincytoskeleton plays a central role in lymphocyte adhesion and motility. Wiskott–Aldrich syndromeprotein (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 actinre-organization in T lymphocytes. We used mice with disruption of the WASP and WIP genes toexamine the role of WASP and WIP in T cell homing. T cell homing to spleen and lymph nodes in vivowas 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 orintegrin-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 inT cells from WIP /  mice and severely reduced in T cells from DKO mice. Cellular F-actin increasefollowing SDF-1a stimulation was normal in WASP /  and WIP /  T cells, but severely reduced inT cells from DKO mice. Actin re-organization and polarization in response to SDF-1a was abnormal inT cells from all knockout mice. Early biochemical events following SDF-1a stimulation that areimportant for chemotaxis and that included phosphorylation of Lck, cofilin, PAK1 and extracellularregulated kinase (Erk) and GTP loading of Rac-1 were examined in T cells from DKO mice and found tobe normal. These results suggest that WASP and WIP are not essential for T lymphocyte rolling andadhesion, but play important and partially redundant roles in T cell chemotaxis in vitro and homingin vivo and function downstream of small GTPases.
PB Oxford University Press
SN 0953-8178
YR 2005
FD 2005
LK http://uvadoc.uva.es/handle/10324/9838
UL http://uvadoc.uva.es/handle/10324/9838
LA eng
NO International Immunology, 2005, vol. 18, n. 2, p. 221-232
NO Producción Científica
DS UVaDOC
RD 22-nov-2024