Abstract

IgE-mediated activation of mast cells and basophils underlies allergic diseases such as asthma. Since Thueson et al. first de-scribed an activity from cultured peripheral blood mononuclear cells that induced the release of histamine from basophils [1], histamine-releasing activities have been studied for more than 30 years. In addition to several cytokines and chemokines with this activity, an unrelated protein termed histamine-releasing factor (HRF) was purified and molecularly cloned by Susan Mac-Donald and her colleagues in 1995 [2]. In this Mini Hot Topic, she describes her pioneering discoveries and others’ findings on HRF functions and gives a historical perspective. HRF, also known as translationally controlled tumor protein (TCTP) and for-tilin, is a highly conserved protein with both intracellular and extracellular functions [3]. Secreted HRF can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. HRF-like activity is found in nasal, skin blister, and bronchoalveolar lavage fluids during the late-phase allergic reactions, which implicates HRF in allergic inflamma-tion [4]. Kyunglim Lee and his associates nicely summarize recent developments on the non-classical pathway-mediated secre-tion of HRF. On the other hand, TCTP has been characterized as a major tumor protein. TCTP is down-regulated upon tumor reversion. In addition, TCTP has a wide range of intracellular functions, including cell cycle progression, proliferation, and survival of a variety of cell types. These functions are related to its ability to work as a guanine nucleotide exchange factorfor Rheb, a Ras superfamily protein and to interact with translational elongation factors eEF1A and eEF1Bβ, antiapoptotic Bcl-2 family proteins, p53, tubulin, and Plk kinase. Ulrich-Axel Bommer elegantly covers recent findings on the molecular mecha-nisms of how TCTP performs its roles in the fundamental biological processes. Two colleagues and I review HRF-interacting molecules emphasizing recent observations on HRF-immunoglobulins interactions. Thus, this Mini Hot Topic covers most of the research area of HRF/TCTP in a timely manner.