Distinct characteristics of signal transduction events by histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced priming and activation of human basophils.
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 FcepsilonRIgamma. 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.
The Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
Becky M
BM
Vonakis
Donald W
DW
Macglashan
Natalia
N
Vilariño
Jacqueline M
JM
Langdon
Rebecca S
RS
Scott
Susan M
SM
MacDonald
D001491:Basophils / Q000166:cytology / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000097:blood; D006636:Histamine Release / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017572:Leukotriene A4 / Q000097:blood; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017455:Receptors, IgE / Q000097:blood; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D000090324:Tumor Protein, Translationally-Controlled 1
D014408:Biomarkers, Tumor; D007377:Interleukin-3; D047908:Intracellular Signaling Peptides and Proteins; D017572:Leukotriene A4; D017455:Receptors, IgE; D011994:Recombinant Proteins; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D002118:Calcium