| Comparison of Ultrastructural Cytotoxic Effects of Carbon and Carbon/Iron Particulates on Human Monocyte-Derived Macrophages John F. Long,1 W. James Waldman,2 Robert Kristovich,3 Marshall Williams,4 Deborah Knight,2 and Prabir K. Dutta3 1Department of Veterinary Biosciences, 2Department of Pathology, 3Department of Chemistry, and 4Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, Ohio, USA 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-µm synthetic carbon-based particulates, designed to simulate environmental particulates of mass median aerodynamic diameter  2.5 µm (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. Key words: carbon, carbon/iron, cytotoxicity, macrophages, ultrastructure. Environ Health Perspect 113:170-174 (2005) . doi:10.1289/ehp.7389 available via http://dx.doi.org/ [Online 22 November 2004]
Address correspondence to J.F. Long, Department of Veterinary Biosciences, Ohio State University, College of Veterinary Medicine, 1925 Coffey Rd., Columbus, OH 43210 USA. Telephone: (614) 688-5940. Fax: (614) 292-6473. E-mail: long.15@osu.edu We thank E. Handley for her work in the preparation of specimens for electron microscopy. This study was supported in part by an Interdisciplinary Seed Grant from the Office of Research, Ohio State University, and National Science Foundation-funded Environmental Molecular Sciences Institute at Ohio State University (CHE 0089147) . The authors declare they have no competing financial interests. Received 17 June 2004 ; accepted 22 November 2004.
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