The role of arachidonic acid metabolism in IL-3-induced proliferation

The role of arachidonic acid metabolites as second messengers in the IL-3-induced activation of DA-1 cells was examined. By using inhibitors of either the cyclooxygenase (CO) or lipoxygenase (LPO) pathways, we determined that neither prostaglandins nor leukotrienes were involved in signal transduction, since aspirin, indomethacin, meclofenamic acid, and nordihydroguaiaretic acid (NDGA) failed to inhibit the proliferation response of DA-1 cells to IL-3. Furthermore, two combination CO/LPO inhibitors, benoxaprofen and BW755c, failed to inhibit DA-1 proliferation. A new CO/LPO compound examined, SK&F 86002, did inhibit proliferation (IC50 = 30 microM +/- 14, N = 11), leading us to conclude this drug has other actions besides CO/LPO inhibition. Finally, direct measurement of 3H-arachidonic acid uptake by DA-1 cells failed to show a difference in the amount of 3H-arachidonic acid incorporated in the presence of limiting or saturating amounts of IL-3. We conclude from these data that arachidonic acid metabolites are not involved in transmembrane signalling by IL-3 in DA-1 cells.