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Characterization of basophil-like cells derived from nonhuman primate bone marrow.

In order to determine whether mast cells or basophils could be derived from nonhuman primate bone marrow, cells from bone marrow aspirates were cultured in the presence of concanavalin A-stimulated nonhuman primate spleen cell supernatants (CAS). Culture conditions were identical to those used for culturing mucosal-like mast cells from mouse bone marrow. In this situation, basophil-like cells (BLC) could be identified in liquid cultures and averaged 14-19 microM in size, were round or oval in appearance, had lobulated nuclei, and contained less than 100 metachromatically staining granules per cell. By electron microscopy, granules had dense oval or semilunar cores with surrounding fibrous whorls. BLC were peroxidase positive, chloroacetate esterase negative, stained positively with acid toluidine blue, and contained 0.1-0.3 pg histamine per cell. BLC expressed IgE receptors and were Leu 5b and Leu 16 negative. IgE-sensitized BLC released histamine after stimulation with antihuman IgE or the calcium ionophore A23187. [35S]-labeled proteoglycans were degraded with chondroitinase ABC but not with heparinase, indicating the absence of heparin in BLC. Thus, culture conditions that include the use of CAS and lead to the growth of mast cells from rodent bone marrow result in the growth of BLC from nonhuman primate bone marrow. These observations suggest that fundamental differences exist in the type of histamine containing cells that arise from rodent and primate bone marrow when such bone marrow cells are cultured under identical conditions.

Animals↗

Changes in the proportions of bronchoalveolar lymphocytes, neutrophils and basophilic cells and the release of histamine and leukotrienes from bronchoalveolar cells in patients with steroid-dependent intractable asthma.

The proportion of inflammatory cells in bronchoalveolar lavage (BAL) fluid and the release of chemical mediators from BAL and peripheral blood cells were examined in 40 patients with steroid-dependent intractable asthma (SDIA) to clarify the effects of a long-term glucocorticoid regimen on these cells. The proportion of BAL lymphocytes was significantly reduced (p < 0.01) and the proportion of BAL neutrophils was significantly increased (p < 0.01) in SDIA patients compared with non-SDIA patients. The proportion of basophilic cells (mast cells and basophils) in BAL fluid was significantly lower in SDIA patients compared to non-SDIA patients (p < 0.02). The values of six ventilatory parameters were significantly lower in SDIA patients with a high proportion of BAL neutrophils (more than 10%) compared with the values in non-SDIA patients. The release of histamine and leukotriene C4 (LTC4) from the BAL cells of patients with atopic asthma was significantly reduced in SDIA patients compared with non-SDIA patients (p < 0.05). These results show that the changes in the proportion of BAL cells are observed in patients with SDIA, and these changes are related to suppressed ventilatory function and a reduction in the release of histamine and LTC4 from BAL cells.

Adult↗

Pharmacologic study of basophil histamine release induced by monocyte chemotactic protein-1 with kinase inhibitors.

Monocyte chemotactic protein-1 (MCP-1)/monocyte chemotactic activating factor has a potent histamine-releasing activity for basophils and is a major component of IgE-independent histamine-releasing factors (HRF). In this study, we examined the effect of a panel of kinase inhibitors on MCP-1-induced histamine release from human basophils to characterize the signaling pathway used by this chemokine. Genistein (3 micrograms/ml), an inhibitor of tyrosine kinase, inhibited MCP-1-induced histamine release by 44%. Wortmannin is a specific inhibitor of phosphatidylinositol 3 kinase (PI-3 kinase). It blocked MCP-1-induced histamine release with an IC50 of 3.3 x 10(-8) M indicating a role of PI-3 kinase in this reaction. KT5926, an inhibitor of myosin light chain kinase, also inhibited histamine release in response to MCP-1 with an IC50 of 10(-6) M. Staurosporine, a potent inhibitor of protein kinase C, although being not specific, augmented MCP-1-induced histamine release by 31.9% at 10(-6) M. These results indicate the possible involvement of a series of kinases, including PI-3 kinase, in the signal transduction pathway used by MCP-1.

Alkaloids↗

Patch-clamp characterization of secretory process in human basophils.

The effects of the intracellular Ca2+ concentration ([Ca2+]i) and a nonhydrolyzable guanosine triphosphate, guanosine 5'-o-(3-thiotriphosphate) (GTP-gamma-S), on secretion were studied by a patch-clamp technique in human basophils. When 10 microM Ca2+ were applied intracellularly, the granules dispersed rapidly, moved vigorously and fused to the cell membrane in 5 min. When the cells were exposed to 2 microM [Ca2+]i and 100 microM GTP-gamma-S, the granules dispersed gradually and granule fusion continued for 7-10 min. The plasma membrane conductance did not appreciably change with either 10 microM [Ca2+]i alone or 2 microM [Ca2+]i + 100 microM GTP-gamma-S. Intracellular application of Ca2+, 1-10 microM, caused a dose-dependent increase in cell membrane capacitance, which reflects granule membrane fusion, indicating exocytosis in a Ca2+ concentration-dependent manner. The addition of 100 microM GTP-gamma-S promoted an increase in the plasma membrane capacitance at concentrations from 0.1 to 2 microM [Ca2+]i and at 2 microM [Ca2+]i the increase was 4.4 times greater than that with 2 microM [Ca2+]i alone. These results indicate that certain G protein(s) promote Ca2+-dependent exocytosis in human basophils.

Basophils↗

Interaction between hyperosmolar and IgE-mediated histamine release from basophils and mast cells.

Because both hyperosmolar and IgE-dependent stimuli may be encountered in the airway, and because hyperosmolarity causes histamine release in basophils, we examined the effects of the 2 stimuli on human lung mast cells. Mast cells prepared by enzymatic digestion of human lung were suspended in buffers made hyperosmolar with mannitol. Significant histamine release was seen above 360 mOsm/kg H2O, increasing to 11.9 +/- 1.0% at 770 mOsm/kg H2O, and release was synergistically enhanced by anti-IgE. Cells that had been rendered unresponsive to IgE-dependent stimuli by exposure to anti-IgE in the absence of Ca++ became markedly more responsive to hyperosmolar stimulation, and released as much as 32 +/- 2% histamine in hyperosmolar buffers alone. Antigen-induced histamine release from the basophils of allergic donors was also synergistically enhanced in buffers above 460 mOsm/kg H2O. These data show that immunologic and nonimmunologic stimuli may interact, and that human lung mast cells are capable of mediator release when exposed to osmolarities that may occur in the airway, especially during hyperventilation. Hyperosmolar mediator release is a plausible mechanism by which exercise-induced hyperventilation might induce asthma.

Antigens↗

Lead poisoning: association with hemolytic anemia, basophilic stippling, erythrocyte pyrimidine 5'-nucleotidase deficiency, and intraerythrocytic accumulation of pyrimidines.

Lead intoxication is accompanied by an acquired deficiency of erythrocyte pryimidine-specific, 5'-nucleotidase. Genetically determined deficiency of this enzyme is associated with chronic hemolysis, marked basophilic stippling of erythrocytes on stained blood films, and unique intraerythrocytic accumulations of pyrimidine-containing nucleotides. The present report documents that lead-induced deficiency when sufficiently severe gives rise to findings similar to the hereditary disorder. Whereas pyrimidine-containing nucleotides are virutally absent in the erythrocytes of normal and reticulocyte-rich blood, 12% of erythrocyte nucloetides in the blood of a patient with lead intoxication contained cytidine. Nucleotidase activity was about 25% that in normal erythrocytes and 15% or less of that expected in comparable reticulocyte-rich blood. The distribution of nucleotidase activity in patient erythrocytes is unknown, and much more severe deficiency could have been present in subsets of the cell populations analyzed. The findings indicate that the hemolytic anemia and increased basophilic stippling characteristic of certain cases of lead intoxication may share a common etiology with essentially identical features of the genetically determined disorder.

Adult↗

Immunologic and nonimmunologic generation of superoxide from mast cells and basophils.

Mediator release from rat peritoneal and human lung mast cells as well as human leukemic basophils was examined to determine whether super-oxide (O(-) (2)) was concomitantly generated. Immunologic or nonimmunologic stimulation of each preparation induced parallel release of histamine and O(-) (2) within 2 min. O(-) (2) production was quantitated by superoxide dismutase (SOD)-inhibitable chemiluminescence and cytochrome c reduction. SOD was detected in basophil and mast cell lysates and was also released by rat mast cells stimulated by anti-IgE. Secretory granules isolated from purified rat mast cells released histamine, O(-) (2), and SOD upon exposure to cations. Thus, both superoxide radicals and SOD may play a role in host defenses involved in immediate hypersensitivity reactions.

Animals↗

Human recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3 cause basophil histamine release.

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.

Basophils↗

Basophilic deposits in the stria vascularis. A clinicopathological update.

Basophilic deposits in the stria vascularis have been found in association with a multitude of disease entities. Their true significance and nature remain obscure. In the temporal bone collection at the Massachusetts Eye and Ear Infirmary are 22 cases with basophilic deposits in the stria vascularis. The ages of the subjects studied ranged from two days to 83 years. Atrophy of the stria vascularis was the main pathology seen in their temporal bones. The deposits were found in both ears in 82% of cases. They tend to show a striking polymorphism. Special histochemical stains suggest they contain glycogen. Hypertension and uremia were two health problems most of the subjects were suffering from during life. A theory is advanced as to the immune complex nature of these deposits. A review of the literature concerning this subject is also offered.

Adolescent↗

Evaluation of granulation peripheral blood basophils in people exposed to industrial contaminants.

The effect of industrial contaminants on the cytomorphometry of basophils was studied. A statistically significant difference in the densification of cytoplasmic granules of basophils was observed in people exposed to pollutants compared to people from less contaminated areas. No differences in cell area, nucleus area, or cytoplasm size were found among the tested groups.

Adult↗

Effects of metal elements on beta-hexosaminidase release from rat basophilic leukemia cells (RBL-2H3).

Immediate allergy is caused by a chemical mediator released from basophile and mast cells via cell degranulation due to reaction between an immunoglobulin E (IgE) antibody, bound with the IgE receptor on the cell membrane, and an antigen. The present authors have established a new method for assaying the enzyme activity of beta-hexosaminidase as an index of chemical mediator release. Using cultured cells instead of conventional methods based on histamine release from mast cells, the present method permits highly accurate mass screening since it uses a well-established cell line of rat basophilic leukemia cells (RBL-2H3). The effects of metal elements on immediate allergic reaction were evaluated using a newly developed assay system. A total of 38 metal elements were investigated for effects on immediate allergic reactions in vitro. These elements were classified by five types on the basis of action on beta-hexosanimidase release: 1) those which showed very strong inhibitory action, such as ZnCl2 and ZrCl4, 2) those which showed relatively strong inhibitory action, such as CdCl2 and CuCl2, 3) those which showed relatively weak inhibitory action, such as CoCl2 and Pb(NO3)2, 4) those which showed neither inhibitory nor promoting action, such as MnCl2 and SrCl2, and 5) AgNO3, which alone showed promoting action.

Animals↗

Identification of a methylated tea catechin as an inhibitor of degranulation in human basophilic KU812 cells.

We examined the constituents of tea that had an inhibitory effect on the degranulation process in the human basophilic cell line, KU812. Among the constituents purified from a extract of 'Benihomare' oolong tea by column chromatography, a methylated (-)-epigallocatechin gallate ((-)-epigallocatechin 3-O-(3-O-methyl) gallate) was found to inhibit the degranulation of KU812 cells that had been stimulated with calcium ionophore A23187. The inhibitory effect of this methylated (-)-epigallocatechin gallate on degranulation was greater than that of (-)-epigallocatechin gallate. This result indicates that methylation of (-)-epigallocatechin gallate may be an effective modification for the catechin to inhibit degranulation from human basophils.

Basophils↗

Cushing's disease in a 5-month infant due to a basophilic microadenoma of the pituitary gland.

We report a female patient who developed severe Cushing's disease during the fifth month of life due to a basophilic pituitary adenoma Histological findings showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis of Cushing's disease. The infant died because of untreatable septic shock. The importance of the present report resides in the age of the child at diagnosis, and that it was the necropsy finding of microadenoma which clarified the cause of the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease is most often diagnosed in children older than 7 years, and our patient was only 5 months old when we detected the pituitary adenoma, the earliest case diagnosed so far. Cushing's syndrome in pediatric patients has been rarely reported and most cases are due to functioning adrenal tumors, usually a malignant carcinoma but occasionally a benign adenoma. The present case shows that the pituitary of these patients should be investigated with important implications in terms of therapeutic approaches, such as pituitary radiotherapy, which can cure the patient when treatment is started very soon.

Adenoma, Basophil↗

Morphological characterization of basophilic cells in bronchoalveolar lavage fluids from patients with bronchial asthma and idiopathic pulmonary fibrosis.

A marked increase in the number of basophilic cells (BCs) was found in the bronchoalveolar lavage (BAL) fluids from the patients with bronchial asthma and idiopathic pulmonary fibrosis (IPF). Histochemical analysis revealed that basophils were the major components of BCs in asthmatic patients, while formalin-insensitive BCs, which are presumed to be connective tissue mast cells, were observed in BAL fluids from IPF patients. In control subjects, almost all of BCs were mucosal mast cells.

Asthma↗

Physiological and clinical studies on norms and variations in counts of circulating basophile leucocytes.

Variations in the counts of circulating basophile leucocytes in 225 subjects were studied. The results obtained are as follows: 1) The counts (per mm3) show a gradual rise with growth, from infancy to adolescence, and maintain a fair constancy in adults. 2) No significant sex difference was found in the peripheral basophile counts. 3) A definite diurnal variation in the counts exists, which is lowest in the morning and highest in the evening. 4) the counts are altered in different phases of the menstrual cycle. 5) Pregnant women show lower counts than nonpregnant women. 6) Surgical trauma and a single electroconvulsive shock lowers the counts significantly but variations are not significant after meals and physical exercise. 7) Smokers have slightly higher counts than non-smokers. 8) course of irradiation therapy lowers the counts significantly in patients with inoperable noplastic diseases. 9) Counts show insignificant variation with alteration of blood glucose level. The results mentioned above are discussed.

Adolescent↗

Regulation of cys-based protein tyrosine phosphatases via reactive oxygen and nitrogen species in mast cells and basophils.

Activation of mast cells and basophils is accompanied by the production of reactive oxygen and nitrogen species that regulate diverse signaling pathways leading to the release of inflammatory mediators and production of a variety of cytokines. Although the functional pathways of reactive oxygen and nitrogen species in vivo are not completely understood, some novel metabolic pathways can be envisioned based on recent findings that protein tyrosine phosphatases can be regulated by reversible oxidation. In this review, we describe major sources and targets of reactive oxide and nitrogen species in mast cells and basophils. Direct and indirect regulations of class I and II Cys-based protein tyrosine phosphatases (LMW-PTP, PTEN, PTP-PEST, SHP-2, PTP1B, PTPalpha, PTPepsilon, DEP-1, TC45, SHP-1, HePTP and LAR) are discussed. The combined data highlight the role of redox-regulated protein tyrosine phosphatases as targets in the development of new ways of therapeutic intervention in allergies and inflammatory diseases.

Animals↗

Basophil histamine release in atopic dermatitis and its relationship to disordered cyclic nucleotide metabolism.

Maximal histamine release (HR) from leucocytes, in response to Concanavalin A (Con A) was significantly higher in a group of 16 adults with moderate to severe atopic dermatitis (AD) when compared to 13 non-atopic adults. In a further 4 adults with AD, HR was similar to that in the normals, suggesting the existence of 'high releaser' and 'low releaser' subsets within the AD group. Leucocyte cyclic AMP phosphodiesterase (PDE) activity was significantly higher in the 'high releaser' group compared to the 'low releaser' and normal groups. High and low HR responses showed strong correlations with high and low PDE. Pre-treatment of leucocytes from 'high releasers' with the experimental PDE PDE inhibitor RO-20-1724 reduced the HR to normal levels. These findings suggest that increased histamine 'releasability' in AD is related to abnormalities in cyclic nucleotide regulation. No significant HR could be demonstrated in response to a range of concentrations of methacholine in 'high releaser' atopics and normals. Methacholine also did not affect HR in response to maximal Con A stimulation in 'high releaser' atopics. Basophil percentages within the leucocyte preparation and the histamine content per basophil, were not significantly different between the atopics and normals. Con A-stimulated histamine release did not correlate significantly with serum IgE levels.

3',5'-Cyclic-AMP Phosphodiesterases↗

Basophils, cytokines, and the allergic inflammatory response.

Immediate allergic response has long been recognized to be related to the activation of mast cells by antigen. The role of the mast cells as producers of cytokines, however, has only more recently been extensively studied. The effect of TH2 lymphocytes in the inflammatory process is now well recognized in animal models. The central role of cytokines in the allergic inflammatory response is currently an area of intense clinical investigation. Cytokines influence production, migration, and activation of basophils. A wide array of cytokines is produced by mast cells upon initiation of the immediate allergic response. These cytokines influence a number of other different cells including basophils and eosinophils, and also activate lymphocytes, thus perpetuating allergic inflammation.

Basophils↗