Degranulation of human basophils by picomolar concentrations of IL-3, IL-5, or granulocyte-macrophage colony-stimulating factor. 1998

W J Lie, and F P Mul, and D Roos, and A J Verhoeven, and E F Knol
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Academic Medical Center, University of Amsterdam.

In most secretory cells, an increase in the cytosolic free Ca2+ concentration ([Ca2+]i) is associated with the exocytosis response. In this study we have evaluated the effect of thapsigargin on histamine release from purified (70% to 97% pure) human basophils of nonallergic donors. Thapsigargin (2 micromol/L), by inhibiting the uptake of Ca2+ in the stores of the endoplasmic reticulum, leads within 1 minute to a gradual increase in [Ca2+]i in human basophils. Incubation of basophils with thapsigargin by itself induced only a very small release of histamine (5.6% +/- 1.8%). However, under suboptimal conditions of stimulation with other agonists, preincubation of basophils with thapsigargin significantly enhanced histamine release. Most strikingly, addition of thapsigargin made basophils extremely sensitive for histamine release induced by IL-3 (maximum histamine release, 71% +/- 7%), IL-5 (maximum histamine release, 43% +/- 8%), or granulocyte-macrophage colony-stimulating factor (GM-CSF) (maximum histamine release, 57% +/- 10%). These cytokines by themselves did not induce histamine release in purified basophils. The effect of thapsigargin was mimicked to a limited extent by addition of platelet-activating factor. We conclude that depletion of the Ca2+ stores may be a critical event in the activation of receptor-mediated histamine release in human basophils.

UI MeSH Term Description Entries
D007377 Interleukin-3 A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Burst-Promoting Factor, Erythrocyte,Colony-Stimulating Factor 2 Alpha,Colony-Stimulating Factor, Mast-Cell,Colony-Stimulating Factor, Multipotential,Erythrocyte Burst-Promoting Factor,IL-3,Mast-Cell Colony-Stimulating Factor,Multipotential Colony-Stimulating Factor,P-Cell Stimulating Factor,Eosinophil-Mast Cell Growth-Factor,Hematopoietin-2,Burst Promoting Factor, Erythrocyte,Colony Stimulating Factor, Mast Cell,Colony Stimulating Factor, Multipotential,Eosinophil Mast Cell Growth Factor,Erythrocyte Burst Promoting Factor,Hematopoietin 2,Interleukin 3,Multipotential Colony Stimulating Factor,P Cell Stimulating Factor
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006636 Histamine Release The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. Histamine Liberation,Histamine Liberations,Histamine Releases
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001491 Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Basophil
D015549 Basophil Degranulation Test An in vitro test used in the diagnosis of allergies including drug hypersensitivity. The allergen is added to the patient's white blood cells and the subsequent histamine release is measured. Basophil Activation Test,Activation Test, Basophil,Activation Tests, Basophil,Basophil Activation Tests,Basophil Degranulation Tests,Degranulation Test, Basophil,Degranulation Tests, Basophil,Test, Basophil Activation,Tests, Basophil Activation
D015848 Interleukin-5 A cytokine that promotes differentiation and activation of EOSINOPHILS. It also triggers activated B-LYMPHOCYTES to differentiate into IMMUNOGLOBULIN-secreting cells. B-Cell Growth Factor-II,Eosinophil Differentiation Factor,IL-5,T-Cell Replacing Factor,BCGF-II,Differentiation Factor, Eosinophil,IL5,T-Cell-Replacing Factor,B Cell Growth Factor II,Interleukin 5,Replacing Factor, T-Cell,T Cell Replacing Factor
D016178 Granulocyte-Macrophage Colony-Stimulating Factor An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. CSF-GM,Colony-Stimulating Factor, Granulocyte-Macrophage,GM-CSF,Histamine-Producing Cell-Stimulating Factor,CSF-2,TC-GM-CSF,Tumor-Cell Human GM Colony-Stimulating Factor,Cell-Stimulating Factor, Histamine-Producing,Colony Stimulating Factor, Granulocyte Macrophage,Granulocyte Macrophage Colony Stimulating Factor,Histamine Producing Cell Stimulating Factor,Tumor Cell Human GM Colony Stimulating Factor

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