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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1789-1796.
Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-07-104364.
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Submitted July 31, 2007
Accepted November 15, 2007
Distinct characteristics of signal transduction events by histamine releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced priming and activation of human basophils
Becky M. Vonakis, Donald W MacGlashan Jr., Natalia Vilarino, Jacqueline M Langdon, Rebecca S. Scott, and Susan M. MacDonald*
Division of Allergy and Clinical Immunolgy, The Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore, MD, United States
* Corresponding author; email: smacdona{at}jhmi.edu.
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, phosphorylation of Akt, MEK, ERK, Syk and Fc RI . 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-responders [HRF/TCTP-R]) have phosphorylation of Syk, Akt, MEK and ERK. Remarkably, basophils from HRF/TCTP-nonresponder donors HRF/TCTP-NR) do not show phosphorylation of these molecules. This finding is different from IL-3, that 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.

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J. M. Langdon, J. T. Schroeder, B. M. Vonakis, A. P. Bieneman, K. Chichester, and S. M. MacDonald
Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced histamine release is enhanced with SHIP-1 knockdown in cultured human mast cell and basophil models
J. Leukoc. Biol.,
October 1, 2008;
84(4):
1151 - 1158.
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