title: Silica and PM1648 modify human alveolar macrophage antigen-presenting cell activity in vitro.
abstract: Some inhaled particles are known to lead to inflammation and lung pathology, whereas others do not appear to have long-term effects. Potential mechanisms to account for these differences are only beginning to be understood. In this article we examine whether silica and PM1648 (a model urban particulate) caused selective deletion of the suppressor human alveolar macrophage (HAM) phenotype (RFD1+/7+), and whether this affected cytokine production in an antigen-presenting cell (APC) assay with autologous T lymphocytes. HAM were exposed to the bioactive particulates, silica and PM1648, for 24 hours, then isolated free of extracellular particulates and nonviable cells; HAM were then cultured with autologous lymphocytes in an 11-day APC assay. Silica exposure up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFN-gamma), and a TH2 lymphocyte-derived cytokine, interleukin-4 (IL-4). PM1648 exposure primarily upregulated IL-4. Neither particle exposure had a significant effect on interleukin-10 (IL-10) production. Control particulate exposures with titanium dioxide (TiO2) and wollastonite (Woll) caused no altered APC activity. Silica and PM1648 demonstrated selective toxicity to suppressor macrophages (RFD1+/7+). We propose that, because of the suppressor macrophage phenotype disabling, the activator macrophage (RFD1+/7-) operates free of the suppressor macrophage's influence, enhancing APC activity with increased lymphocyte-derived proinflammatory cytokine production.
authors.affiliation: University of Texas Medical School, Department of Internal Medicine, Houston, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Hamilton
authors.forename: J C
authors.initials: JC
authors.lastname: Pfau
authors.forename: G D
authors.initials: GD
authors.lastname: Marshall
authors.forename: A
authors.initials: A
authors.lastname: Holian
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D017610:Calcium Compounds / Q000633:toxicity*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D017640:Silicates / Q000633:toxicity*; D012822:Silicon Dioxide / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*
chemical_list: D000395:Air Pollutants, Occupational; D017610:Calcium Compounds; D017640:Silicates; C009495:titanium dioxide; D015847:Interleukin-4; D012822:Silicon Dioxide; D007371:Interferon-gamma; D014025:Titanium; C031293:calcium silicate