title: Comparison of ultrastructural cytotoxic effects of carbon and carbon/iron particulates on human monocyte-derived macrophages.
abstract: In this study, we tested the hypothesis that the presence of iron in carbon particulates enhances ultrastructural perturbation in human monocyte-derived macrophages (MDMs) after phagocytosis. We used 1-microm synthetic carbon-based particulates, designed to simulate environmental particulates of mass median aerodynamic diameter < or = 2.5 microm (PM2.5). Cultures of human MDMs or T-lymphocytes (as a nonphagocytic control) were exposed to carbon or carbon/iron particulates for various time periods and examined by transmission electron microscopy for ultrastructural changes. T-cells failed to internalize either of the particulates and showed no organelle or nuclear changes. Conversely, MDMs avidly phagocytized the particulates. MDMs treated with C particulates exhibited morphologic evidence of macrophage activation but no evidence of lysis of organelles. In contrast, MDMs treated with C/Fe particulates exhibited coalescence of particulate-containing lysosomes. This phenomenon was not observed in the case of C particulates. By 24 hr there was a tendency of the C/Fe particulates to agglomerate into loose or compact clusters. Surrounding the compact C/Fe agglomerates was a uniform zone of nearly total organelle lysis. The lytic changes diminished in proportion to the distance from the agglomerate. In such cells, the nucleus showed loss of chromatin. Although C particles induced no detectable oxidative burst on treated MDMs, C/Fe particles induced a nearly 5-fold increase in the extracellular oxidative burst by treated MDMs compared with untreated controls. Iron bound to C particles catalyzed the decomposition of hydrogen peroxide to generate hydroxyl radicals. Results of these studies suggest that, among particulates of similar size, biologic activity can vary profoundly as a function of particulate physicochemical properties.
authors.affiliation: Department of Veterinary Biosciences, Ohio State University, Columbus, Ohio 43210, USA. long.15@osu.edu
authors.forename: John F
authors.initials: JF
authors.lastname: Long
authors.forename: W James
authors.initials: WJ
authors.lastname: Waldman
authors.forename: Robert
authors.initials: R
authors.lastname: Kristovich
authors.forename: Marshall
authors.initials: M
authors.lastname: Williams
authors.forename: Deborah
authors.initials: D
authors.lastname: Knight
authors.forename: Prabir K
authors.initials: PK
authors.lastname: Dutta
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D002244:Carbon / Q000633:toxicity*; D002478:Cells, Cultured; D006801:Humans; D007501:Iron / Q000633:toxicity*; D008163:Luminescent Measurements; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D016897:Respiratory Burst / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D000393:Air Pollutants; D002244:Carbon; D007501:Iron