Differences between the Effects of f-Met-Leu-Phe and Leukotriene B4 on Phosphoinositide Turnover and Their Relationship to Calcium Mobilization and Protein Kinase C Activation
It is generally accepted that the mobilization and metabolism of arachidonic acid are involved in the activation and/or modulation of the neutrophil’s responses and that the major biological activities of arachidonic acid are mediated by the ability of leukotriene B4 to alter calcium homeostasis (for a review and original citations, see Bach, 1983). This conclusion is based on various experimental results. First, the biological activities of exogenously added arachidonic acid and some of its metabolites have been demonstrated. Second, the activation of the neutrophils by chemotactic factors can be modulated by certain lipase and lipoxygenase inhibitors. Third, chemotactic factors cause the release of arachidonic acid previously incorporated in phospholipids and stimulate its subsequent metabolism including the generation of leukotriene B4. Fourth, the exogenous addition of leukotriene B4 to neutrophils increases the intracellular concentration of free calcium, with characteristics similar to those of its biological activities. This increase occurs through the release of calcium from internal stores, by displacement of previously bound calcium from membranous and other sites, and from the extracellular medium through an increase in the plasma membrane permeability to calcium.
KeywordsArachidonic Acid Phosphatidic Acid Free Calcium Chemotactic Factor Calcium Mobilization
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