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Physiological and Pharmacological Regulation of Prostaglandin and Leukotriene Production by Macrophages
Author(s) -
Bonney Robert J.,
Humes John L.
Publication year - 1984
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.35.1.1
Subject(s) - arachidonic acid , diacylglycerol lipase , phospholipase a2 , biology , diacylglycerol kinase , biochemistry , zymosan , prostaglandin , lipid signaling , phospholipase , arachidonate 5 lipoxygenase , leukotriene , cyclooxygenase , pharmacology , enzyme , protein kinase c , immunology , asthma , in vitro
The synthesis and secretion of prostaglandins and leukotrienes by mouse peritioneal macrophages is under several regulatory controls. Arachidonic acid must first be released from phospholipid stores by the action of phospholipases. Macrophages have the capacity to deacylate arachidonic acid directly from the SN 2 position of phospholipids via the action of a phospholipase A 2 . In addition, these cells contain a phospholipase C capable of removing inositolphosphate from phosphatidylinositol generating diacylglycerol. Another enzyme, diacylglycerol lipase is present to then generate arachidonic acid. The free arachidonic acid then enters the cyclooxygenase pathway to generate prostaglandins, the lipoxygenase pathway to generate leukotrienes or both pathways. The nature of the inflammatory stimulus added to these cells determines which of the above pathways become operative. Zymosan and the Ca + + ionophore, A23187 stimulate the synthesis of both prostaglandins and leukotrienes whereas phorbol myristate acetate and lipopolysaccharide induce only the synthesis of prostaglandins. In addition, the synthesis of these two products by macrophages can be regulated by certain antiinflammatory compounds. Indomethacin, aspirin, ibuprofen and benoxaprofen are only inhibitors of the prostaglandin pathway, whereas BW755C, 5,8,11 ETYA, NDGA and sulindac sulfide (high doses) are inhibitors of the synthesis of both prostaglandins and leukotrienes. Dapsone, an effective drug for leprosy, also inhibits the synthesis of both of these products.