Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine-releasing factors (HRFs) are a group of cytokines that cause histamine release (HR) from basophils and mast cells. The concept of the priming effect of cytokines and the heterogeneity of IgE involved in the HRF-induced HR have been emphasized in recent years. In this study, we performed a series of experiments to elucidate the above-mentioned hypotheses. The stock HRF were obtained by stimulating mononuclear cells (MNC) with phytohemagglutinin (PHA). Maximal activity was observed 36 hr after culture. By gel filtration, HRF was eluted with a peak activity ranging from 12 to 18 KD. A large portion (75%) of HRF activity could be neutralized by a combination of antibodies against interleukin 1 (IL-1), IL-3, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). The stimulation of basophils with 100 ng/ml each of IL-3, IL-6, IL-7, GM-CSF, or TNF-alpha alone caused 10% HR; however, when the cells were pretreated with 10 ng/ml of either IL-3, IL-6, IL-7, IL-8, TNF-alpha, or GM-CSF and then stimulated with anti-IgE, a marked increase in HR was regularly observed. The combination of 100 ng/ml each of IL-1, IL-3, IL-8, GM-CSF, and TNF-alpha could induce only about 20% HR; furthermore, such combinations did not have an additive or synergistic priming effect on anti-IgE-induced HR compared to the effect of single cytokines. Stripping of surface-bound IgE with lactic acid markedly reduced the capacity of basophils to release histamine in response to MNC-HRF and anti-IgE. Passive sensitization of IgE-stripped basophils with high-HRF responders' serum could restore their responsiveness to both MNC-HRF and anti-IgE, but passive sensitization with low-HRF responders' serum could restore responsiveness to anti-IgE only. Moreover, passage of MNC-HRF through high-, but not low-HRF, responders' IgE-Sepharose columns significantly reduced the HR activity of MNC-HRF. Finally, although the eluant could induce only 10% HR, the majority of its HR activity could be restored by the addition of effluent but not by the mixture of IL-1, IL-3, IL-8, GM-CSF, and TNF-alpha, suggesting the presence of a complex interaction among those cytokines. In summary, MNC-HRF contained at least two types of HRF activity; one was IgE dependent and the other was IgE independent.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterization of histamine-releasing activity: role of cytokines and IgE heterogeneity. 138 Sep 65

Histamine-releasing factors (HRFs) have been shown to be released from a variety of human cells, including T lymphocytes and alveolar macrophages. We considered the possibility that known cytokines might possess such activity on human basophils and/or mast cells and therefore tested preparations of human recombinant IL 3, IL 4, IL 5, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) upon a panel of basophil donors. IL 3 and GM-CSF possessed significant histamine-releasing activity in 8 of 10 and 12 of 14 subjects, respectively. In each instance, a dose response could be demonstrated. IL 4 and G-CSF had no such activity, whereas IL 5 had activity in only 2 of 14 donors tested. We conclude that IL 3 and GM-CSF represent two effective HRFs, and suggest that HRF, as isolated based upon histamine-releasing activity, is likely to be heterogeneous in terms of molecular identity. Whether previously described HRFs relate specifically to IL 3 or GM-CSF must await primary sequence analysis of HRF and/or studies with monospecific antisera.
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PMID:Human recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3 cause basophil histamine release. 245 33

We have purified and further characterized a histamine releasing factor (HRF) derived from human mononuclear cells using gel-filtration HPLC, reverse-phase HPLC, anion exchange chromatography, and elution from SDS gels after electrophoresis. Considerable heterogeneity is seen, far exceeding that published in prior reports. Gel filtration HPLC yielded a major peak at molecular weight 30,000 and minor peaks at 50,000 and 12,000. Reverse-phase HPLC gave one major fraction in the void volume and an eluted peak at 50-60% acetonitrile. Accell QMA anion exchange HPLC revealed three peaks of activity; one in the void volume similar to that published previously using QAE-Sephadex, and peaks that eluted at 0.5 and 0.8 M ammonium acetate, respectively. Electroelution following SDS-PAGE yielded peaks at MW 12,000 and 15-17,000 plus variable peaks at 25-27,000, 31-34,000, and 80-90,000 D. Using a combination of the aforementioned procedures, we have purified molecular species of HRF at 41,000 and 17,000 D to apparent homogeneity, as judged by SDS PAGE and autoradiography. Since human interleukin 3 and granulocyte-macrophage colony-stimulating factor possess histamine-releasing capability, it is clear that multiple cytokines can share this activity. However, the major HRF we isolate from human mononuclear cells appears, thus far, to be unique.
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PMID:Purification and further characterization of human mononuclear cell histamine-releasing factor. 246 21