THE EFFECTS OF EICOSANOID BIOSYNTHESIS INHIBITORS ON PROPHENOLOXIDASEACTIVATION, PHAGOCYTOSIS AND CELL SPREADING IN GALLERIA-MELLONELLA

The invertebrate immune system produces melanotic nodules in response to bacterial infections and this has previously been shown to be media ted by eicosanoids, Nodulation occurs in two phases: the first involve s hemocyte degranulation and activation of the prophenoloxidase cascad e; the second involves formation of a cellular capsule by attachment a nd spreading of hemocytes, We demonstrate that inhibitors of eicosanoi d biosynthesis affect both of these phases of nodulation in Galleria m ellonella. The phospholipase A(2) inhibitor, dexamethasone, as well as the cyclooxygenase inhibitor, indomethacin, significantly inhibit pha gocytosis in vitro and prophenoloxidase activation in vivo. The inhibi tory effects of dexamethasone were abolished by the addition of exogen ous arachidonic acid, Furthermore, 5,8,11,14-eicosatetraynoic acid, de xamethasone and indomethacin inhibit hemocyte spreading in vitro, The findings support the idea that eicosanoid derivatives mediate both pha ses of the nodulation response and are consistent with previous studie s which attribute roles for eicosanoids in other species as modulators of cell activity. (C) 1997 Elsevier Science Ltd.