Capacitative Ca2+ influx and activation of the neutrophil respiratory burst. Different regulation of plasma membrane- and granule-localized NADPH-oxidase
| Autor: | Marie Samuelsson, Anna Karlsson, Daniel Granfeldt |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Thapsigargin
Neutrophils Immunology Cytoplasmic Granules chemistry.chemical_compound Lanthanum Extracellular Immunology and Allergy Channel blocker Egtazic Acid Respiratory Burst Oxidase test NADPH oxidase biology Superoxide Cell Membrane NADPH Oxidases Cell Biology Respiratory burst Enzyme Activation chemistry Biochemistry biology.protein Biophysics Calcium Calcium Channels Intracellular Signal Transduction |
| Zdroj: | Journal of leukocyte biology. 71(4) |
| ISSN: | 0741-5400 |
| Popis: | The neutrophil NADPH-oxidase may be activated in the plasma membrane, resulting in release of oxygen metabolites extracellularly, or in the granule or phagosomal membranes, giving intracellular production of oxidants. An increase in [Ca2+]i mediated through binding of fMLF to its receptor is part of a signaling cascade that activates the plasma membrane-localized oxidase. In contrast, a rise in [Ca2+]i induced by a Ca2+ ionophore results in activation of the intracellular pool of oxidase. We mimicked fMLF-induced emptying of intracellular Ca2+ stores with thapsigargin. This induced a pronounced intracellular oxidase activity but no extracellular release of oxidants. The thapsigargin-induced effect was dependent on capacitative Ca2+ influx, because the effect was inhibited dose-dependently by EGTA and the Ca2+ channel blocker La3+. At La3+ concentrations between 200 and 400 μM, thapsigargin also induced a massive extracellular production of superoxide anion. No other channel blockers tested induced a similar effect. We conclude that elevation in [Ca2+]i by capacitative Ca2+ influx induces NADPH-oxidase activation at an intracellular site. Further, activation of the plasma membrane-localized NADPH-oxidase is regulated by a more complex Ca2+ signaling, involving capacitative Ca2+ influx and possibly the specific action of La3+-sensitive Ca2+ channels. |
| Databáze: | OpenAIRE |
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