title: Characterization of histamine-releasing activity: role of cytokines and IgE heterogeneity.
abstract: 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)
authors.affiliation: Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Republic of China.
authors.forename: T N
authors.initials: TN
authors.lastname: Liao
authors.forename: K H
authors.initials: KH
authors.lastname: Hsieh
mesh_terms: D001491:Basophils / Q000276:immunology; D014408:Biomarkers, Tumor; D002852:Chromatography, Ion Exchange; D016207:Cytokines / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006636:Histamine Release / Q000276:immunology*; D006801:Humans; D007126:Immunoglobulin Allotypes; D007073:Immunoglobulin E / Q000276:immunology* / Q000302:isolation & purification; D007378:Interleukins / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008222:Lymphokines / Q000276:immunology / Q000302:isolation & purification; D008233:Lymphotoxin-alpha / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D007126:Immunoglobulin Allotypes; D007378:Interleukins; D008222:Lymphokines; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D000090324:Tumor Protein, Translationally-Controlled 1; D007073:Immunoglobulin E