Human Histamine Releasing Factor Research Articles

Crystal structures of murine and human Histamine-Releasing Factor (HRF/TCTP) and a model for HRF dimerisation in mast cell activation

In allergic disease, mast cell activation is conventionally triggered by allergen-mediated cross-linking of receptor-bound IgE on the cell surface. In addition to its diverse range of intracellular roles in apoptosis, cell proliferation and cancer, Histamine-Releasing Factor (HRF) also activates mast cells and basophils. A subset of IgE antibodies bind HRF through their Fab regions, and two IgE binding sites on HRF have been mapped. HRF can form dimers, and a disulphide-linked dimer is critical for activity. The current model for the activity of HRF in mast cell activation involves cross-linking of receptor-bound IgE by dimeric HRF, mediated by HRF/Fab interactions. HRF crystal and solution structures have provided little insight into either the formation of disulphide-linked HRF dimers or the ability of HRF to activate mast cells. We report the first crystal structure of murine HRF (mHRF) to 4.0Å resolution, revealing a conserved fold. We also solved the structure of human HRF (hHRF) in two new crystal forms, one at the highest resolution (1.4Å) yet reported. The high resolution hHRF structure reveals a disulphide-linked dimer, in which the two molecules are closely associated, and provides a model for the role of both human and murine HRF in mast cell activation.

Immunological cross-reactivity analysis on recombinant histamine-releasing factors from Schistosoma japonicum, Clonorchis sinensis, and Wistar rat

Studies have demonstrated a declined incidence of allergic disorders in the population with helminthic infection. Though several hypotheses have been proposed to explain how helminthic infection protected people against allergies, the underlying mechanisms remain poorly understood. A human histamine-releasing factor (HRF) has been proved to be closely related to the development of allergic disorders and the homologues are ubiquitously expressed in all eukaryotic organisms including parasites. To study the role of this HRF in the relationship between parasitic infection and allergic diseases with experimental model of rats, the cDNA of the homologues of the human HRF from Wistar rat, Schistosoma japonicum, and Clonorchis sinensis containing a coding region of 519, 510, and 510 bp, respectively, were cloned. In addition, the cross-reactivity between recombinant rat HRF (rRHRF) and recombinant S. japonicum HRF (rSjHRF) as well as that between rRHRF and recombinant C. sinensis HRF (rCsHRF) was identified with ELISA and Western blotting. Based on their detected cross-reactivities, a hypothesis was put forward that the anti-parasitic HRFs antibodies could inhibit the effects of host HRF and those of parasitic HRFs and thus decreased the host sensitivities to allergens.

Atopy and asthma genes--where do we stand?

Atopy and asthma genes--where do we stand?

Chromosomal localization1 of tumor protein, translationally-controlled 1 (TPT1) encoding the human histamine releasing factor (HRF) to13q12→q14

The human histamine releasing factor (HRF; http://www. ncbi.nlm.nih.gov/htbin-post/Omin/dispim?600763) also called tumor protein, translationally controlled 1 (TPT1; http://www. gdb.org/) causes histamine release from basophils of certain allergic donors (MacDonald et al., 1995). It has identity to the translationally controlled tumor protein (TCTP, an alias for TPT1) which was previously designated as p23 (Bohm et al., 1989), and is highly conserved from man to alfalfa plants. While originally described as a growth-related tumor protein, it has also been identified in healthy liver tissue (Hughes et al., 1993) and more recently in macrophages, platelets, keratinocytes, erythrocytes, hepatocytes as well as tumor cells (Sanchez et al., 1997). The biologic function of TPT1 remained illusive until HRF was shown to cause histamine release from a subset of allergic donors’ basophils (MacDonald et al., 1995). We proposed that HRF produced this secretion by interaction with a subpopulation of IgE molecules that we termed IgE+. By definition, basophils expressing IgE– on their surface, did not support mediator release when stimulated with HRF. In a subsequent study, we were able to show that HRF enhanced IgE-dependent IL-4 and IL-13 secretion from all basophils (Schroeder et al., 1997). More recently, we have demonstrated that HRF promotes cytokine secretion and a calcium response in purified human eosinophils (Bheekha-Escura and MacDonald, manuscript submitted). Here we report the mapping of the gene encoding HRF (TPT1) to chromosome 13q12→q14. Of interest is the report showing a linkage on chromosome 13 of loci D13S270 and D13S153 to atopy via sibpair analysis (Daniels et al., 1996). Due to the fact that HRF activates cells important in the allergic diathesis, it’s gene could potentially be a candidate gene for allergies including allergic asthma. Therefore, it would be of considerable interest to determine if TPT1 maps close to those loci.

Relationship of one form of human histamine releasing factor (HRF) to connective tissue activating peptide-III (CTAP-III): [formula omitted]∗. State University of New York∗, Stony Brook, NY, and University of Michigan +, Ann Arbor, MI

Relationship of one form of human histamine releasing factor (HRF) to connective tissue activating peptide-III (CTAP-III): [formula omitted]∗. State University of New York∗, Stony Brook, NY, and University of Michigan +, Ann Arbor, MI

Histamine release from mast cells of various species induced by histamine releasing factor from human lymphocytes

The aim of our work was to investigate the effect of histamine releasing factor (HRF), produced in vitro by lymphocytes obtained from atopic and non-atopic asthmatics, on mast cells of various species (mouse - peritoneal mast cells, hamster and rat - peritoneal and pleural mast cells, guinea-pig - mesenteric and pulmonary mast cells). We found that human HRF is able to release histamine from the examined mast cell populations in a dose-dependent fashion. Mast cells from various species differed in their susceptibility to the action of HRF; rat pleural and guinea-pig mesenteric and pulmonary mast cells were the most susceptible, while mouse and hamster peritoneal mast cells - the least susceptible. The presence of 50% D2O in the medium significantly increased HRF-induced histamine release from rat mast cells, while the addition of phosphatidylserine did not change it. HRF-induced histamine release from guinea-pig mesenteric mast cells was not related to sensitization of these cells. We also compared histamine release from guinea-pig pulmonary and mesenteric mast cells induced by human HRF produced in vitro by lymphocytes obtained from atopic and non-atopic asthmatics. We have found that supernatant from atopic asthmatics lymphocyte cultures released significantly more histamine than supernatant from non-atopic asthmatics lymphocyte cultures. Our studies give evidence that human HRF acts across the species barrier and induces histamine release from mast cells of various species. The mechanism of HRF action on mast cells seems to be different from that of allergen.

Histamine releasing factor is not an interferon

The speculation that human histamine releasing factor (HRF) - a lymphokine that releases histamine from human tissues, might be the same as gamma-interferon was investigated. The speculation arose from the fact that HRF and gamma-interferons are both lymphokines and have both been reported to affect histamine release from human basophils. Using purified gamma-interferons either naturally obtained or E. coli-derived (recombinant DNA technique), as well as alpha-, alpha-2, arg, and beta-interferons, it was found that: Unlike HRF, the interferons neither induced histamine release nor affected antigen-induced histamine release from human basophils in vitro. HRF is partially acid-stable whereas gamma-interferon is acid labile. HRF samples had little interferon activity which did not correlate with HRF activity. The estimated molecular weight of HRF is 12,000-18,000 daltons and contrasts to those of interferons, which exceed 30,000 daltons. The results strongly suggest that HRF is very unlikely to be a gamma-interferon or indeed any other class of interferon.

A histamine-releasing factor from activated human mononuclear cells.

Human mononuclear cells activated by streptokinase-streptodornase have been shown to elaborate a factor capable of releasing histamine from human basophils. We have developed reproducible methods for its production in large quantities by using cells obtained from leukapheresis packs, by detection utilizing donor basophils known to release well with anti IgE, and by quantitation of histamine by the radioenzyme method. Human histamine-releasing factor (HRF) gave a single peak upon gel filtration with an estimated m.w. of 32,000; SDS gel electrophoresis revealed a single major band as seen at m.w. 30,000. HRF can be resolved into at least two forms separable by ion-exchange chromatography on QAE Sephadex, and two peaks of activity were obtained by chromatofocusing or isoelectric focusing in gels at pH 6.9 and between 7.4 and 8.3. This factor represents an important potential link between cellular immunity and immediate hypersensitivity.

Action of the human lymphokine histamine releasing factor on mouse peritoneal mast cells

Histamine releasing factor (HRF) — a human lymphokin≐ — has been shown previously to release histamine from basophils in vitro. In this paper we show that HRF acted across the species barrier and released histamine from mouse peritoneal mast cells. This response was dose-dependent. Mast cells from both sensitized and non-sensitized mice were equally susceptible to the action of HRF. We observed synergistic action of HRF with specific allergen (ovalbumin) or HRF with anti-IgE antibody in releasing histamine from mast cells. Preincubation of mast cells with calcium ion chelating agent ethylenediaminetetraacetic acid (EDTA) or disodium cromoglycate induces only a small inhibition of histamine release caused by HRF. We conclude that histamine release from mouse peritoneal mast cells can serve as an in vitro test for the assay of human HRF.