L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: Implications for cellular activation during adhesion and migration

Ziqiang Ding, Thomas B. Issekutz, Gregory P. Downey, Thomas K. Waddell

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

97 Citas (Scopus)

Resumen

L-selectin mediates leukocyte tethering and rolling, the first step in a sequential process of leukocyte adhesion and migration. Additionally, L-selectin has important signaling roles perhaps contributing to leukocyte activation and integrin-mediated adhesion. Because chemokines are critically involved in leukocyte activation, we questioned whether L-selectin signaling affects chemokine receptor expression and function. We observed that whereas only 5% to 15% of freshly isolated lymphocytes expressed CXCR4 on the cell surface, intracellular CXCR4 was detectable in all cells. Engagement of L-selectin by antibody cross-linking or the L-selectin ligands fucoidan or sulfatide mobilized intracellular CXCR4 to significantly increase surface CXCR4 expression but did not affect CCR5, CCR7, or β2-integrin expression. L-selectin stimulation also inhibited stromal-derived factor 1 (SDF-1)-induced CXCR4 internalization. The combined effects of L-selectin on CXCR4 trafficking are likely important in markedly enhancing cell activation by SDF-1. Blockade of SDF-1-induced CXCR4 internalization resulted in enhanced actin polymerization on subsequent exposure to SDF-1. Physiologically more important, L-selectin stimulation increased SDF-1-induced lymphocyte adhesion and transendothelial migration, which were inhibited by anti-leukocyte function-associated antigen 1 antibodies, tyrosine kinase inhibitors, and pertussis toxin. To further corroborate the additive stimulating effects, L-selectin signaling and SDF-1 increased β2-integrin activation. Taken together, L-selectin-mediated signals specifically enhance CXCR4 expression and function, suggesting a novel mechanism for the modulation of lymphocyte activation during cell adhesion and transmigration.

Idioma originalEnglish
Páginas (desde-hasta)4245-4252
Número de páginas8
PublicaciónBlood
Volumen101
N.º11
DOI
EstadoPublished - jun. 1 2003

ASJC Scopus Subject Areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Huella

Profundice en los temas de investigación de 'L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: Implications for cellular activation during adhesion and migration'. En conjunto forman una huella única.

Citar esto