title: Differential requirements for cellular cytoskeleton in human macrophage complement receptor- and Fc receptor-mediated phagocytosis.
abstract: We investigated the requirement for cellular cytoskeleton in CR- and FcR-mediated phagocytosis by human monocyte-derived macrophages (M phi). Inhibition of actin microfilament (MF) assembly and stability by cytochalasins B and D completely inhibited M phi phagocytosis of sheep E coated with C3b (EC3b), iC3b (EC3bi), and IgG (EIgG) via CR1, CR3, and FcR, respectively. Ligand-binding to either CR or FcR was not effected by cytochalasins. Nocodazole (NOC), which prevents microtubule (MT) polymerization, and taxol, which causes random polymerization of MT inhibited M phi phagocytosis of EC3b(i) but not EIgG. However, the combination of taxol (5 x 10(-4) M) and NOC (2 x 10(-6) M) augmented M phi CR-mediated phagocytosis. In addition, agents known to increase intracellular cGMP augmented phagocytosis of EC3b(i). Conversely, agents that increase intracellular cAMP inhibited CR-mediated phagocytosis. These agents had no effect on FcR-mediated phagocytosis, and did not effect ligand-binding to CR or FcR. PMA markedly enhanced CR- but not FcR-mediated phagocytosis, and augmentation of CR-mediated phagocytosis by PMA was inhibited by both CD and NOC. In contrast, the synthetic diacylglycerol, 1-oleoyl-2-acetoyl-sn-3-glycerol augmented, and inhibitors of protein kinase C inhibited M phi phagocytosis via CR and FcR. These data indicate that for adherently cultured human M phi: 1) binding of ligand-coated E to CR or FcR does not require an intact cytoskeleton; 2) intact actin microfilament are required for phagocytosis via CR and FcR; 3) phagocytosis via CR1 and CR3 but not FcR is dependent on MT assembly; 4) PMA most likely augments CR-mediated phagocytosis through promotion of MT assembly; and 5) PKC activity is involved in the phagocytic signal generated by both CR and FcR.
authors.affiliation: Department of Internal Medicine, University of Cincinnati College of Medicine, OH 45267.
authors.forename: S L
authors.initials: SL
authors.lastname: Newman
authors.forename: L K
authors.initials: LK
authors.lastname: Mikus
authors.forename: M A
authors.initials: MA
authors.lastname: Tucci
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008870:Microtubules / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology; D011951:Receptors, Complement / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D011951:Receptors, Complement; D011961:Receptors, Fc; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate