Distinct characteristics of signal transduction events by histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)–induced priming and activation of human basophils

• Published in: Blood 2008-02, Vol.111 (4), p.1789-1796
• Main Authors: Vonakis, Becky M., MacGlashan, Donald W., Vilariño, Natalia, Langdon, Jacqueline M., Scott, Rebecca S., MacDonald, Susan M.
• Format: Article
• Language: English
• Subjects: Basophils - cytology; Basophils - physiology; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - physiology; Calcium - blood; Chemokines, Cytokines, and Interleukins; Hematologic and hematopoietic diseases; Histamine Release - physiology; Humans; Interleukin-3 - physiology; Intracellular Signaling Peptides and Proteins - metabolism; Leukotriene A4 - blood; Medical sciences; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Receptors, IgE - blood; Recombinant Proteins - metabolism; Signal Transduction; Syk Kinase
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-07-104364

We previously identified a negative correlation between histamine release to histamine releasing factor/translationally controlled tumor protein (HRF/TCTP) and protein levels of the Src homology 2 domain–containing inositol 5′ phosphatase (SHIP) in basophils. We have also demonstrated that HRF/TCTP primes basophils to release mediators. The purpose of this study was to begin characterization of signal transduction events directly induced by HRF/TCTP and to investigate these events when HRF/TCTP is used as a priming agent for human basophil histamine release. Highly purified human basophils were examined for surface expression of bound HRF/TCTP, changes in calcium, and phosphorylation of Akt, mitogen-activated protein kinase kinase (MEK), extracellular signal–regulated kinase (ERK), Syk, and FcϵRIγ. Results showed that basophils from all donors bound HRF/TCTP. There was a biphasic calcium response to HRF/TCTP, which corresponded to the magnitude of histamine release. Furthermore, those donors who have direct histamine release when exposed to HRF/TCTP (HRF/TCTP responder [HRF/TCTP-R] donors) have phosphorylation of Syk, Akt, MEK, and ERK. Remarkably, basophils from HRF/TCTP-nonresponder (HRF/TCTP-NR) donors do not show phosphorylation of these molecules. This finding is different from IL-3, which also primes basophils for histamine release, but does show phosphorylation of these events. We conclude that priming induced by HRF/TCTP is distinct from that induced by IL-3.