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(Journal of Leukocyte Biology. 2001;70:776-782.)
© 2001 by Society for Leukocyte Biology

Regulation of the very late antigen-4-mediated adhesive activity of normal and nonreleaser basophils: roles for Src, Syk, and phosphatidylinositol 3-kinase

Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131

Correspondence: Ronald P. Andrews, Department of Pathology, University of New Mexico, School of Medicine, CRF Building, Rm. 203, 2325 Camino de Salud, Albuquerque, NM 87131. Email: randrews{at}salud.unm.edu

Normal human basophils express the integrin, VLA-4, and cross-linking their high-affinity IgE receptor, FcRI, increases their VLA-4-dependent adhesion to VCAM-1-transfected Chinese hamster ovary (CHO) cells. Here we show that the FcRI-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 FcRI-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 FcRI cross-linking to VLA-4 up-regulation. Both Src and Syk-regulated components of adhesion may be impaired in nonreleaser basophils.

Key Words: signal transduction • tyrosine kinase • Lyn • human

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