title: Asbestos and silica-induced changes in human alveolar macrophage phenotype.
abstract: The mechanism by which fibrogenic particulates induce inflammation that can progress to lung fibrosis is uncertain. The alveolar macrophage (AM) has been implicated in the inflammatory process because of its function and reported release of inflammatory mediators when isolated from fibrotic patients. It has been recently shown that fibrogenic, but not nonfibrogenic, particulates are highly potent in inducing apoptosis of human AM. In this study, we tested the hypothesis that fibrogenic particulates could shift the phenotypic ratio of human AM to a more inflammatory condition. The macrophage phenotypes were characterized by flow cytometry targeting the RFD1 and RFD7 epitopes. Results demonstrated that chrysotile and crocidolite asbestos, as well as crystalline silica, but not titanium dioxide or wollastonite, increased the RFD1+ phenotype (inducer or immune activator macrophages) and decreased the RFD1+ RFD7+ phenotype (suppressor macrophages). These results provide a mechanistic explanation that may link apoptosis (namely, suppressor macrophages) to a shift in the ratio of macrophage phenotypes that could initiate lung inflammation.
authors.affiliation: Department of Internal Medicine, University of Texas Houston Health Science Center, Houston 77030, USA. aholian@heart.med.uth.tmc.edu
authors.forename: A
authors.initials: A
authors.lastname: Holian
authors.forename: M O
authors.initials: MO
authors.lastname: Uthman
authors.forename: T
authors.initials: T
authors.lastname: Goltsova
authors.forename: S D
authors.initials: SD
authors.lastname: Brown
authors.forename: R F
authors.initials: RF
authors.lastname: Hamilton
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001194:Asbestos / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D000939:Epitopes / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016676:Macrophages, Alveolar / Q000187:drug effects*; D010641:Phenotype; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D000939:Epitopes; D001194:Asbestos; D012822:Silicon Dioxide