Arachidonic acid is essential for IgG Fc receptor-mediated phagocytosis by human monocytes.
Phagocytosis is a specialized function of neutrophils and macrophages that requires coordination of multiple biochemical and biophysical events. Considerable progress has been made in identifying the membrane receptors involved in phagocytosis, but the intracellular signaling pathways that are necessary for particle ingestion are poorly understood. In an effort to address this complex question, we investigated the role of arachidonic acid (AA) in the uptake of yeast and IgG-coated E (EIgG) or C-coated E. Human monocytes, labeled with 3H AA, released this label during phagocytosis of yeast and EIgG, but not in response to EC3b. The PL inhibitors bromophenacyl bromide and manoalide abolished the release of 3H and inhibited phagocytosis of EIgG in parallel. Both drugs caused a similar inhibition of yeast-mediated 3H release but had little effect on yeast ingestion. Similar results were obtained with the inhibitor quinacrine (mepacrine). Exogenously added AA and dihomo-gamma-linolenic acid restored bromophenacyl bromide-inhibited EIgG ingestion; arachidonate analogs eicosatrienoic acid and eicosapentanoic acid did not. Inhibition of the cyclooxygenase and lipoxygenase pathways for AA metabolism by indomethacin or BW755C did not affect EIgG phagocytosis, demonstrating that these major AA metabolic pathways are not involved in phagocytic signaling. These experiments suggest that release of AA is essential for EIgG ingestion and that phagocytosis in monocytes proceeds by at least two mechanisms, one dependent on AA (EIgG) and one independent of it (yeast).
Lennartz
M R
MR
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Brown
E J
EJ
D000098:Acetophenones / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D003179:Complement C3b / Q000378:metabolism; D015777:Eicosanoids / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D066298:In Vitro Techniques; D009000:Monocytes / Q000502:physiology*; D010587:Phagocytosis; D010740:Phospholipases / Q000037:antagonists & inhibitors; D011796:Quinacrine / Q000494:pharmacology; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000494:pharmacology; D015003:Yeasts / Q000276:immunology
D000098:Acetophenones; D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D001095:Arachidonic Acids; D015777:Eicosanoids; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D013729:Terpenes; D016718:Arachidonic Acid; D003179:Complement C3b; C045673:manoalide; D010740:Phospholipases; D011796:Quinacrine; C006821:4-bromophenacyl bromide