Multiple defects in Fc epsilon RI signaling in Syk-deficient nonreleaser basophils and IL-3-induced recovery of Syk expression and secretion

• Published in: The Journal of immunology (1950) Vol. 165; no. 10; pp. 5913 - 5920
• Main Authors: Kepley, C L, Youssef, L, Andrews, R P, Wilson, B S, Oliver, J M
• Format: Journal Article
• Language: English
• Published: United States 15.11.2000
• Subjects: AFc receptors; Antibodies, Anti-Idiotypic - metabolism; Basophils - immunology; Basophils - metabolism; Basophils - ultrastructure; Cell Adhesion - immunology; Enzyme Precursors - biosynthesis; Enzyme Precursors - deficiency; Enzyme Precursors - genetics; Enzyme Precursors - metabolism; Humans; Immunoglobulin E - immunology; Integrin alpha4beta1; Integrins - physiology; Interleukin-3 - physiology; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - biosynthesis; Intracellular Signaling Peptides and Proteins; Protein-Tyrosine Kinases - biosynthesis; Protein-Tyrosine Kinases - deficiency; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Receptors, IgE - immunology; Receptors, IgE - metabolism; Receptors, IgE - physiology; Receptors, Lymphocyte Homing - physiology; Receptors, Very Late Antigen - physiology; RNA, Messenger - metabolism; Syk Kinase; Syk protein; Up-Regulation - immunology; VLA-4 antigen
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.10.5913

Human basophils respond to Ag-induced cross-linking of their high affinity IgE receptor, FcepsilonRI, by releasing histamine and other mediators from granules, producing IL-4 and other cytokines and, as shown in this study, by forming membrane ruffles and showing increased very late Ag-4 (VLA-4)-mediated adhesion to VCAM-1-expressing target cells. We have identified five blood donors whose basophils lack detectable levels of the FcepsilonRI-associated protein tyrosine kinase, Syk. Despite showing no obvious ultrastructural differences from normal basophils, nonreleaser basophils fail to form membrane ruffles, to show increased VLA-4-mediated adhesive activity, or to produce IL-4 in response to FcepsilonRI cross-linking. Although Syk protein levels are suppressed in basophils from all five donors, Syk mRNA is consistently present. Furthermore, culturing nonreleaser basophils for 4 days with IL-3 restores Syk protein expression and FcepsilonRI-mediated histamine release. Understanding the reversible suppression of Syk protein expression in nonreleaser basophils, and learning to replicate this property in patients with allergic inflammation could be a powerful and specific way to limit symptomatic disease.