Regulation of the very late antigen-4-mediated adhesive activity of normal and nonreleaser basophils: roles for Src, Syk, and phosphatidylinositol 3-kinase.
J Leukoc Biol
; 70(5): 776-82, 2001 Nov.
Article
em En
| MEDLINE
| ID: mdl-11698498
ABSTRACT
Normal human basophils express the integrin, VLA-4, and cross-linking their high-affinity IgE receptor, FcepsilonRI, increases their VLA-4-dependent adhesion to VCAM-1-transfected Chinese hamster ovary (CHO) cells. Here we show that the FcepsilonRI-mediated up-regulation of normal basophil VLA-4 adhesion is abolished by the Src inhibitor, PP1, the Syk inhibitor, ER-27319, and the phosphatidylinositol 3-kinase inhibitor, wortmannin. PP1, but not ER-27319 or wortmannin, also reduces basal adhesion and adhesion stimulated by chemotactic peptide, by Ca(++) ionophores, and by phorbol myristate acetate (PMA). Nonreleaser basophils (the consistently Syk-deficient, variably Lyn-deficient, severely degranulation-impaired cells found in about 10% of donors) share the PP1 phenotype of lowered basal adhesion, no FcepsilonRI-mediated adhesion up-regulation, and reduced adhesive responses to chemoattractant ionophores and PMA. These results implicate Src kinases in the control of basal VLA-4 activity and place Syk and phosphatidylinositol 3-kinase in the pathway linking FcepsilonRI cross-linking to VLA-4 up-regulation. Both Src and Syk-regulated components of adhesion may be impaired in nonreleaser basophils.
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Base de dados:
MEDLINE
Assunto principal:
Basófilos
/
Proteínas Tirosina Quinases
/
Transdução de Sinais
/
Integrinas
/
Receptores de Retorno de Linfócitos
/
Quinases da Família src
/
Fosfatidilinositol 3-Quinases
/
Precursores Enzimáticos
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article