サイクリックAMPによる食細胞の活性酸素産生抑制機構

抄録

Superoxide anion and arachidonic acid were produced in guinea pig neutrophils in response to a chemotactic peptide (fMLP). Both responses were markedly, but the former response to a phorbol ester was not at all, inhibited when the cellular cAMP level was raised by prostaglandin E₁ combined with a cAMP-phosphodiesterase inhibitor. Increasing cAMP was also inhibitory to fMLP-induced activation of phosphatidylinositol (PI) 3-kinase and Ca²⁺ influx without any effect on the cation mobilization from intracellular stores. The fMLP-induced respiratory burst was abolished when PI 3-kinase was inhibited by wortmannin or LY294002, but was not affected when Ca²⁺ influx was inhibited. On the contrary, fMLP released arachidonic acid from the cells treated with the PI 3-kinase inhibitors as well as from non-treated cells, but it did not so when cellular Ca²⁺ uptake was prevented. The chemotactic peptide activated PI 3-kinase even in cells in which the receptormediated intracellular Ca²⁺ mobilization and respiratory burst were both abolished by exposure of the cells to a permeable Ca²⁺ chelating agent. Thus, stimulation of fMLP receptors gave rise to dual effects, activation of PI 3-kinase and intracellular Ca²⁺ mobilization; both effects were necessary for the fMLP-induced respiratory burst. Increasing cellular cAMP inhibited the respiratory burst and arachidonic acid release as a result of the inhibitions of PI 3-kinase and Ca2+ influx, respectively, in fMLP-treated neutrophils.