Arachidonate metabolic pathways in cells harvested from rat pleural cavity at various times after carrageenan...

Cells were harvested from rat pleural cavity before and during the inflammatory response stimulated by carrageenan injection. The conversion of [14C]arachidonate by intact cells into products of the cyclooxygenase and 5-lipoxygenase pathways was studied in the absence and presence of ionophore. Incorporation of arachidonate into phosphatidic acid was also followed. In the absence of ionophore, the principal arachidonate metabolites of resident macrophages were the cyclooxygenase products, prostacyclin and thromboxane, while mobilized monocytes produced thromboxane as a major product, but very little prostacyclin. Arachidonate-metabolizing enzymes in mobilized monocytes were, in general, less active than those of resident macophages. Cells harvested at times when mobilized neutrophils were the predominant cell type were capable of converting arachidonate into thromboxane and prostaglandins, but not prostacyclin. These cells exhibited the most active turnover of arachidonate into phosphatidic acid, and the extent of this turnover appeared to be temporally related to the presence of edema in the pleural cavity at the time of cell harvest. Enzymatic formation of 5-lipoxygenase products was dependent on calcium and was markedly stimulated by ionophore A23187 in both resident and mobilized pleural cells. Among several non-steroidal drugs tested, cyclooxygenase inhibitors were the most effective in preventing the inflammatory response in the carrageenan model of inflammation.