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 MM6 with human monocytes. MM6 expressed FcgammaRI at levels similar to monocytes, whereas FcRgammaII expression was approximately double. MM6 ingested IgG-opsonized erythrocytes (EIgG) in a calcium-independent manner. Incubation of MM6 with bromoenol lactone, an inhibitor of the phagocytic phospholipase (pPL), coordinately decreased phagocytosis and pPL activity. This inhibition was overcome by exogenous arachidonic acid, suggesting that phagocytosis requires pPL activation and arachidonic acid release. MM6 phagocytosis was inhibited with staurosporine and activated with diacylglycerol, supporting a role for protein kinase C (PKC) in this process. The pPL activators mastoparan and melittin restored phagocytosis to PKC-inhibited cells, suggesting that pPL lies downstream from PKC. These results suggest that the MM6 signal transduction pathway for IgG-mediated phagocytosis is similar to that of monocytes (PKC-->pPL-->arachidonic acid-->phagocytosis). The results are discussed in the context of the finding that MM6 exhibit low phagocytosis relative to monocytes and thus may represent an attractive cell line for molecular manipulation in "recovery of function" studies.
Karimi
K
K
Department of Physiology and Cell Biology, Albany Medical College, New York 12208-3479, USA.
Gemmill
T R
TR
Lennartz
M R
MR
D001095:Arachidonic Acids / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D054522:Group VI Phospholipases A2; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000276:immunology; D008555:Melitten / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D009895:Opsonin Proteins / Q000378:metabolism; D010455:Peptides; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000494:pharmacology*; D017452:Receptors, IgG / Q000096:biosynthesis; D012397:Rosette Formation; D014862:Wasp Venoms / Q000494:pharmacology
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D009895:Opsonin Proteins; D010455:Peptides; D017452:Receptors, IgG; D014862:Wasp Venoms; D008555:Melitten; C037500:mastoparan; D011493:Protein Kinase C; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human