PROSTAGLANDIN E(2) RELEASE TRIGGERED BY PHAGOCYTOSIS OF LATEX-PARTICLES - A DISTINCT ASSOCIATION WITH PROSTAGLANDIN SYNTHASE ISOZYMES IN BONE-MARROW MACROPHAGES

Previous studies showed that murine bone marrow-derived macrophages (M phi) induced in vitro by IL-3 express cellular prostaglandin G/H synthase (PGHS)-1 but not PGHS-2. To induce PGHS-2 in this study, the M phi were primed further with IFN-gamma plus LPS. The expression of the PGHS isozymes was determined by cytometric analysis using Abs against PGHS-1 and PGHS-2. The expression of PGHS-2, but not PGHS-1, was dexamethasone-sensitive. To assess PGE(2)-releasing capacity, the primed M phi were triggered by challenge with calcium ionophore A23187, the protein kinase C (PKC) activator PMA, exogenous arachidonic acid, and 1.1-mu m latex bead particles. Our results showed that the primed M phi expressed both isozymes and responded to all challenges used to release a substantial amount of PGE(2) (> 10 ng PGE(2)/10(6) cells/ml), whereas the control unprimed M phi responded to A23187 and arachidonic acid but not to PMA or latex beads to release PGE(2). However, the primed M phi did not release PGE, when triggered with nonphagocytosable particles (greater than or equal to 40 mu m) or when pretreated with cytochalasin D before they were challenged with 1.1-mu m beads. Furthermore, staurosporine, a PKC inhibitor, did not inhibit the PGE(2) release triggered by the beads. PMA-triggered PGE(2) release by the primed M phi, in sharp contrast, was staurosporine-sensitive but cytochalasin D-resistant. Our data suggest that there are multiple or alternative pathways for triggering PGE(2) synthesis and release distinctively associated with two PGH synthase isozymes. It is of special interest that the novel pathway triggered by interiorization of particles is associated with the expression of PGHS-2.