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Arachidonic Acid Release Is Closely Related to the Fc γ Receptor‐Mediated Superoxide Generation in Macrophages
Author(s) -
Ida Eiichi,
Sakata Atsuko,
Tominaga Mari,
Yamasaki Hisato,
Onoue Kaoru
Publication year - 1988
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.1988.tb01477.x
Subject(s) - arachidonic acid , protein kinase c , biology , phospholipase a2 , biochemistry , superoxide , pharmacology , kinase , enzyme
Stimulation of macrophages with IgG2 immune complexes induced dose‐dependently the O 2 − generation and the release of arachidonic acid and its metabolites. This Fc γ R‐mediated O 2 − generation was inhibited by a phospholipase A 2 inhibitor, 4‐ p ‐bromophenacyl bromide (4‐pBPB), in parallel to the dose‐dependent inhibition of arachidonic acid release. The main arachidonic acid metabolites released were shown to be prostaglandin E 2 and thromboxane B 2 and blocking of the production of these metabolites by indomethacin did not inhibit the O 2 − generation. Inhibition of the Fc γ R‐mediated O 2 − generation and the arachidonic acid release by the C‐kinase inhibitor, 1‐(5‐isoquinolinesulfonyl)‐2‐methylpiperazine (H‐7), was less intense than by 4‐pBPB. These results support the previously proposed hypothesis that arachidonic acid acts as an intracellular activator of the Fc γ R‐mediated O 2 − generation in macrophages. Although the C‐kinase activation may also contribute to the activation of the O 2 − ‐generating system, arachidonic acid release appears to play a major role in Fc γ R‐mediated O 2 − generation. In contrast, activation of C‐kinase seems to be contributing mainly in the induction of both the arachidonic acid release and O 2 − generation by 12‐ o ‐tetradecanoylphorbol 13‐acetate (TPA). Furthermore, suboptimal concentrations of TPA and arachidonate were found to act synergistically to stimulate O 2 − generation and the inhibition study suggested a positive synergism between C‐kinase and arachidonic acid release to induce O 2 − generation. This synergistic action may have general importance in receptor‐mediated O 2 − generation.