title: Protein kinase C agonists enhance phagocytosis of P. aeruginosa by murine alveolar macrophages.
abstract: Pulmonary alveolar macrophages (AMphis) are incompetent to phagocytose unopsonized Pseudomonas aeruginosa, but ingestion by other macrophage phenotypes (i.e., peritoneal macrophages) occurs efficiently. The purpose of this study was to explore factors that might control such phenotypic differences. Our laboratory has demonstrated that AMphis exposed to sodium azide display enhanced phagocytosis of P. aeruginosa. Here we report that the phagocytic-enhancing effect of sodium azide was abrogated by inhibitors of protein kinase C (PKC). Furthermore, the addition of PKC agonists, such as phorbol myristate acetate (PMA), and tumor necrosis factor alpha (TNF-alpha), mimicked the phagocytic enhancing effect of sodium azide. We conclude that AM4phis are normally incompetent to phagocytose P. aeruginosa. Factors that up-regulate AMphi function (azide, PMA, TNF-alpha) can reverse the phagocytic incompetence in vitro. Although these compounds are not appropriate candidate therapeutic agents, their effects provide insights for understanding of the pathways responsible for regulation of P. aeruginosa phagocytosis.
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, Canada. jpheale@interchange.ubc.ca
authors.forename: J P
authors.initials: JP
authors.lastname: Heale
authors.forename: D P
authors.initials: DP
authors.lastname: Speert
mesh_terms: D000818:Animals; D002273:Carcinogens; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D019810:Sodium Azide / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002273:Carcinogens; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019810:Sodium Azide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate