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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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CHEMOKINES, CYTOKINES, AND INTERLEUKINS

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. Vonakis1, Donald W. MacGlashan, Jr1, Natalia Vilariño1, Jacqueline M. Langdon1, Rebecca S. Scott1, and Susan M. MacDonald1

1 The Johns Hopkins Asthma and Allergy Center, Baltimore, MD

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 Fc{epsilon}RI{gamma}. 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.


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