Protein kinase C and a calcium-independent phospholipase are required for IgG-mediated phagocytosis by Mono-Mac-6 cells

Mono-Mac-6 (MM6) human monocytes ingest IgG-opsonized particles better than other human cell Lines. We compared the phagocytic signaling pathway in MM 6 with human monocytes, MM6 expressed Fc gamma RT. at levels similar to mon ocytes, whereas FcR gamma II expression Tvas approximately double. MM6 inge sted IgG-opsonized erythrocytes (EIgG) in a calcium-independent manner. inc ubation of MM6 with bromoenol lactone, an inhibitor of the phagocytic phosp holipase (pPL), coordinately decreased phagocytosis and pPL activity. This inhibition was overcome by exogenous arachidonic acid, suggesting that phag ocytosis requires pPL activation and arachidonic acid release. MM6 phagocyt osis was inhibited with staurosporine and activated with diacylglycerol, su pporting a role for protein kinase C (PKC) in this process. The pPL activat ors mastoparan and melittin restored phagocytosis to PKC-inhibited cells, s uggesting that pPL lies downstream from PKC. These results suggest that the MM6 signal transduction pathway for IgG-mediated phagocytosis is similar t o that of monocytes (PKC-->pPL-->arachidonic acid-->phagocytosis), The resu lts are discussed in the context of the finding that MM6 exhibit low phagoc ytosis relative to monocytes and thus may represent an attractive cell line for molecular manipulation in "recovery of function" studies.