title: Ambient air particulates stimulate alveolar macrophages of smokers to promote differentiation of myeloid precursor cells.
abstract: Studies from our laboratory have shown that exposure to air pollution particles smaller than 10 microm (PM10) induced a systemic inflammatory response that includes the release of granulocytes from the bone marrow. In the present study we tested the hypothesis that mediators released from human alveolar macrophages (AM) exposed to PM10 accelerate the maturation of granulocyte precursors. Human myeloid precursor cells (HL60 cells) were incubated with the supernatant from AM exposed to PM10. Phagocytosis of PM10 by AM resulted in the production of cytokines, particularly interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < .05). The supernatant from AM exposed to PM10 did not influence myeloid cell proliferation but promoted cell differentiation as measured by surface GD11b and CD14 expressions compared to control supernatant (P < .05). This effect of exposed-AM supernatants on myeloid cell differentiation was blocked by anti-IL-6 monoclonal antibodies (CD11b and CD14; P < .05) and anti-GM-CSF monoclonal antibodies (CD14, P < .01). We conclude that human AM exposed to PM10 produce mediators, particularly IL-6 and GM-CSF that promote the differentiation of bone marrow myeloid cells and we speculate that these cytokines are involved in the release of granulocytes from the bone marrow associated with exposure to air pollution particulates.
authors.affiliation: McDonald Research Laboratory, University of British Columbia, St Paul's Hospital, Vancouver, Canada.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Suwa
authors.forename: James C
authors.initials: JC
authors.lastname: Hogg
authors.forename: Renaud
authors.initials: R
authors.lastname: Vincent
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.forename: Stephan F
authors.initials: SF
authors.lastname: van Eeden
mesh_terms: D000368:Aged; D000393:Air Pollutants / Q000633:toxicity*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D017077:Culture Media, Conditioned; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000502:physiology; D018922:HL-60 Cells; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000393:Air Pollutants; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D016177:Macrophage-1 Antigen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor