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Regulation of the very late antigen‐4‐mediated adhesive activity of normal and nonreleaser basophils: roles for Src, Syk, and phosphatidylinositol 3‐kinase
Author(s) -
Andrews Ronald P.,
Kepley Christopher L.,
Youssef Lama,
Wilson Bridget S.,
Oliver Janet M.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.5.776
Subject(s) - wortmannin , syk , phosphatidylinositol , biology , microbiology and biotechnology , lyn , proto oncogene tyrosine protein kinase src , kinase , src family kinase , tyrosine kinase , signal transduction
Normal human basophils express the integrin, VLA‐4, and cross‐linking their high‐affinity IgE receptor, FcɛRI, increases their VLA‐4‐dependent adhesion to VCAM‐1‐transfected Chinese hamster ovary (CHO) cells. Here we show that the FcɛRI‐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 FcɛRI‐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 FcɛRI cross‐linking to VLA‐4 up‐regulation. Both Src and Syk‐regulated components of adhesion may be impaired in nonreleaser basophils.