TY - JOUR
T1 - A comparison of asbestos and urban particulate matter in the in vitro modification of human alveolar macrophage antigen-presenting cell function
AU - Hamilton, Raymond F.
AU - Holian, Andrij
AU - Morandi, Maria T.
N1 - Funding Information:
Received 7 July 2003; accepted 23 September 2003. This work was funded in part by National Institutes of Health grants ES-04804 and ES-11120, as well as the Environmental Protection Agency grant R826782. Address correspondence to Andrij Holian, PhD, Center for Environmental Health Sciences, SB154, Department of Pharmaceutical Sciences, University of Montana, 32 Campus Drive, Missoula, MT 59812, USA.
PY - 2004/3
Y1 - 2004/3
N2 - The mechanism for how inhaled particles cause or exacerbate human diseases is not known. It is clear, however, that some particles are more bioactive than others. One possible mechanism may involve a modification of antigen-presenting cell function. In this study, 2 forms of asbestos (crocidolite and Libby amphibole) and PM2.5 (an urban particle) were cultured with human alveolar macrophages (HAMs) to determine whether antigen-presenting cell (APC) function was altered. HAMs were exposed to the bioactive particles, asbestos and PM2.5, for 24 hours, then isolated free of extracellular particulates and nonviable cells. Isolated HAMs were then cultured with autologous lymphocytes in an 11-day APC assay using tetanous toxoid as the antigen and the resulting culture supernatants were assayed for lymphocyte-derived cytokines. Asbestos exposure, regardless of type, up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFNγ), and the TH2 lymphocyte-derived cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13). PM2.5 exposure up-regulated all 3 cytokines also. Although cytokine production levels were significantly higher for the treatment compared to control cultures as a group, there was extreme variability in the responses between subjects. In addition, there was no correlation between an individual's cells' response to asbestos verses PM, suggesting that more than one possible mechanism exists for a particle-induced APC effect and individual differential sensitivities to inhaled bioactive particles. This work supports the hypothesis that some inhaled particles can modify immune function by directly affecting APCs thus up-regulating the normal lymphocyte response to antigens in the lung.
AB - The mechanism for how inhaled particles cause or exacerbate human diseases is not known. It is clear, however, that some particles are more bioactive than others. One possible mechanism may involve a modification of antigen-presenting cell function. In this study, 2 forms of asbestos (crocidolite and Libby amphibole) and PM2.5 (an urban particle) were cultured with human alveolar macrophages (HAMs) to determine whether antigen-presenting cell (APC) function was altered. HAMs were exposed to the bioactive particles, asbestos and PM2.5, for 24 hours, then isolated free of extracellular particulates and nonviable cells. Isolated HAMs were then cultured with autologous lymphocytes in an 11-day APC assay using tetanous toxoid as the antigen and the resulting culture supernatants were assayed for lymphocyte-derived cytokines. Asbestos exposure, regardless of type, up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFNγ), and the TH2 lymphocyte-derived cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13). PM2.5 exposure up-regulated all 3 cytokines also. Although cytokine production levels were significantly higher for the treatment compared to control cultures as a group, there was extreme variability in the responses between subjects. In addition, there was no correlation between an individual's cells' response to asbestos verses PM, suggesting that more than one possible mechanism exists for a particle-induced APC effect and individual differential sensitivities to inhaled bioactive particles. This work supports the hypothesis that some inhaled particles can modify immune function by directly affecting APCs thus up-regulating the normal lymphocyte response to antigens in the lung.
KW - IL-13
KW - IL-4
KW - Interferon gamma
KW - Macrophage subpopulations
KW - PM
UR - http://www.scopus.com/inward/record.url?scp=1442311068&partnerID=8YFLogxK
U2 - 10.1080/01902140490266439
DO - 10.1080/01902140490266439
M3 - Article
C2 - 14972774
AN - SCOPUS:1442311068
SN - 0190-2148
VL - 30
SP - 147
EP - 162
JO - Experimental Lung Research
JF - Experimental Lung Research
IS - 2
ER -
