Effects of PM10 in human peripheral blood monocytes and J774 macrophages

Respiratory Research

V Stone²  K Donaldson¹  DM Brown² 

[1] ELEGI Laboratory, Wilkie Building, University of Edinburgh, UK;School of Life Sciences, Napier University, Edinburgh, UK

关键词: PM₁₀;    Cytoskeleton;    Cytokine;    Nanoparticle;    Macrophage;   

Others  :  1227347
DOI  :  10.1186/1465-9921-5-29

 received in 2004-09-29, accepted in 2004-12-21,  发布年份 2004

【 摘 要 】

The effects of PM₁₀, one of the components of particulate air pollution, was investigated using human monocytes and a mouse macrophage cell line (J774). The study aimed to investigate the role of these nanoparticles on the release of the pro-inflammatory cytokine TNF-α and IL-1α gene expression. We also investigated the role of intracellular calcium signalling events and oxidative stress in control of these cytokines and the effect of the particles on the functioning of the cell cytoskeleton. We showed that there was an increase in intracellular calcium concentration in J774 cells on treatment with PM₁₀ particles which could be significantly reduced with concomitant treatment with the calcium antagonists verapamil, the intracellular calcium chelator BAPTA-AM but not with the antioxidant nacystelyn or the calmodulin inhibitor W-7. In human monocytes, PM₁₀ stimulated an increase in intracellular calcium which was reduced by verapamil, BAPTA-AM and nacystelyn. TNF-α release was increased with particle treatment in human monocytes and reduced by only verapamil and BAPTA-AM. IL-1α gene expression was increased with particle treatment and reduced by all of the inhibitors. There was increased F-actin staining in J774 cells after treatment with PM₁₀ particles, which was significantly reduced to control levels with all the antagonists tested. The present study has shown that PM₁₀ particles may exert their pro-inflammatory effects by modulating intracellular calcium signalling in macrophages leading to expression of pro-inflammatory cytokines. Impaired motility and phagocytic ability as shown by changes in the F-actin cytoskeleton is likely to play a key role in particle clearance from the lung.

【 授权许可】

   
2004 Brown et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Pope CA, Dockery DW: Epidemiology of particle effects. In Air Pollution and Health. Edited by Holgate ST, Samet JM, Koren HS, Maynard RL. Academic Press, San Diego; 1999:673-705.
• [2]Brunekreef B, Holgate ST: Air pollution and health. Lancet 2002, 360:1233-1242.
• [3]Lighty JS, Veranth JM, Sarofim AF: Combustion aerosols: factors governing their size and composition and implications to human health. J Air Waste Manag Assoc 2000, 50:1565-1618.
• [4]Ferin J, Oberdoster G, Penney DP: Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol 1992, 6:535-542.
• [5]Schwartz J: Daily deaths are associated with combustion particles rather than SO(2) in philadelphia [In Process Citation]. Occup Environ Med 2000, 57:692-697.
• [6]Seaton A, MacNee W, Donaldson K, Godden D: Particulate air pollution and acute health effects. Lancet 1995, 345:176-178.
• [7]Utell MJ, Frampton MW: Acute health effects of ambient air pollution: The ultrafine particle hypothesis. J Aerosol Med 2000, 13:355-359.
• [8]Dasenbrock C, Peters L, Creutzenberg O, Heinrich U: The carcinogenic potency of carbon particles with and without PAH after repeated intratracheal administration in the rat. Toxicol Lett 1996, 88:15-21.
• [9]Driscoll KE, Carter JM, Howard BW, Hassenbein DG, Pepelko W, Baggs RB, Oberdoster G: Pulmonary inflammation, chemokine, and mutagenic responses in rats after subchronic inhalation of carbon black. Toxicol Appl Pharmacol 1996, 136:372-380.
• [10]Oberdoster G, Ferin J, Lehnert BE: Correlation between particle-size, in-vivo particle persistence, and lung injury. Environ Health Perspect 1994, 102:173-179.
• [11]Nikula KJ, Snipes MB, Barr EB, Griffith WC, Henderson RF, Mauderly JL: Comparative pulmonary toxicities and carcinogenicities of chronically inhaled diesel exhaust and carbon black in F344 rats. Fundam Appl Toxicol 1995, 25:80-94.
• [12]Donaldson K, Tran CL: Inflammation caused by particles and fibres. Inhal Toxicol 2002, 14:5-27.
• [13]Drouet C, Shakhov AN, Jongeneel CV: Enhancers and transcription factors controlling the inducibility of the tumor-necrosis-factor-alpha promoter in primary macrophages. J Immunol 1991, 147(5):1694-1700.
• [14]Rhoades KL, Golub SH, Economou JS: The regulation of the human tumor-necrosis-factor-alpha promoter region in macrophage, t-cell, and b-cell lines. J Biol Chem 1992, 267(31):22102-22107.
• [15]Sayeed MM: Alterations in calcium signaling and cellular responses in septic injury. New Horizons 1996, 4:72-86.
• [16]Hoyal CR, Giron-Calle J, Forman HJ: The alveolar macrophage as a model of calcium signaling in oxidative stress. J Toxicol Environ Health B Crit Rev 1998, 1:117-134.
• [17]Faux SP, Michelangeli F, Levy LS: Calcium chelator quin-2 prevents crocidolite-induced DNA strand breakage in human white blood cells. Mutat Res 1994, 311:209-215.
• [18]Stone V, Brown DM, Watt N, Ritchie H, Wilson M, Donaldson K: Ultrafine particle-mediated activation of macrophages: intracellular calcium signaling and oxidative stress. Inhal Toxicol 2000, 12(suppl 3):345-351.
• [19]Ding A, Sanchez E, Nathan CF: Taxol shares the ability of bacterial lipopolysaccharide to induce tyrosine phosphorylation of microtubule-associated protein kinase. J Immunol 1993, 151:5596-5602.
• [20]Hwang S, Ding A: Activation of NF-Kappa B in murine macrophages by taxol. Cancer Biochem Biophys 1995, 14:265-272.
• [21]Valerius NH, Stendahl OI, Hartwig JH, Stossel TP: Distribution of actin-binding protein and myosin in neutrophils during chemotaxis and phagocytosis. Adv Exp Med Biol 1982, 141:19-28.
• [22]McCulloch CA, Knowles GC: Deficiencies in collagen phagocytosis by human fibroblasts in vitro: a mechanism for fibrosis? J Cell Physiol 1993, 155:461-471.
• [23]Horowitz MA: The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J Exp Med 1983, 158:2108-2126.
• [24]Powell JJ, Harvey RS, Ashwood P, Wolstencroft R, Gershwin ME, Thompson RPH: Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease. J Autoimmun 2000, 14:99-105.
• [25]Casini-Raggi V, Kam L, Chong YJ, Fiocchi C, Pizarro TT, Cominelli F: Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. J Immunol 1995, 154:2434-2440.
• [26]Lovett D, Kozan B, Hadam M, Resch K, Gemsa D: Macrophage cytotoxicity: interleukin 1 as a mediator of tumor cytostasis. J Immunol 1986, 136:340-347.
• [27]Navarro S, Debili N, Bernaudin JF, Vainchenker W, Doly J: Regulation of the expression of IL-6 in human monocytes. J Immunol 1989, 142(12):4339-4345.
• [28]Dinarello CA: Interleukin-1 and Interleukin-1 antagonism. Blood 1991, 77(8):1627-1652.
• [29]Dinarello CA, Wolff SM: The role of interleukin-1 in disease. New Engl J Med 1993, 328:106-113.
• [30]Stone V, Shaw J, Brown DM, MacNee W, Faux SP, Donaldson K: The role of oxidative stress in the prolonged inhibitory effect of ultrafine carbon black on epithelial cell function. Toxicol In vitro 1998, 12:649-659.
• [31]Dransfield I, Buckle AM, Savill JS, McDowall A, Haslett C, Hogg N: Neutrophil apoptosis is associated with a reduction in CD 16 (FcγRIII) expression. J Immunol 1994, 153:1254-1263.
• [32]Grynkiewicz G, Poenie M, Tsien RY: A new generation of Ca2+ indicators with greatly improved fluorescent properties. J Biol Chem 1985, 260:3440-3450.
• [33]Stone V, Tuinman M, Vamvakopoulos JE, Shaw J, Brown DM, Petterson S, Faux SP, Borm P, MacNee W, Michaelangeli F, Donaldson K: Increased calcium influx in a monocytic cell line on exposure to ultrafine carbon black. Eur Respir J 2000, 15:297-303.
• [34]Moeller W, Brown DM, Stone V, Kreyling WG: Ultrafine particles cause cytoskeletal dysfunctions in macrophages: role of intracellular calcium. Toxicol Appl Pharmacol 2004, in press.
• [35]Brown DM, Donaldson K, Borm PJ, Schins RPF, Denhart M, Gilmour PS, Stone V: Calcium and ROS-mediated activation of transcription factors and TNF-α cytokine gene expression in macrophages exposed to ultrafine particles. Am J Physiol Lung Cell Mol Physiol 2004, 286:L344-L353.
• [36]Pope CA: Epidemiology of fine particulate air pollution and human health: biologic mechanisms and Who's at risk? Environ Health Perspect 2000, 108(Suppl 4):713-723.
• [37]Bates DJ: Health indices of the adverse effects of air pollution: The question of coherence. Environ Res 1992, 59:336-349.
• [38]Schwartz J: Air pollution and daily mortality: A review and meta-analysis. Environ Res 1994, 64:36-52.
• [39]Donaldson K, Stone V, Seaton A, MacNee W: Ambient particle inhalation and the cardiovascular system: Potential mechanisms. Environ Health Perspect 2001, 109(Suppl 4):523-527.
• [40]Donaldson K, MacNee W: Potential mechanisms of adverse pulmonary and cardiovascular effects of particulate air pollution (PM10). Int J Hyg Environ Hlth 2001, 203:411-415.
• [41]Wilson MR, Lightbody JH, Donaldson K, Sales J, Stone V: Interactions between ultrafine particles and transition metals in vivo and in vitro. Toxicol Appl Pharmacol 2002, 184:172-179.
• [42]Malorni W, Iosi F, Mirabelli F, Bellomo G: Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells. Alterations underlying surface bleb formation. Chemico-Biological Interactions 1991, 80(2):217-236.
• [43]Gilmour PS, Brown DM, Lindsay TG, Beswick PH, MacNee W, Donaldson K: Adverse health effects of PM(10) particles: Involvement of iron in generation of hydroxyl radicals. Occup Environ Med 1996, 53(12):817-822.
• [44]O'Reilly PJ, Philip J, Hickman-Davis JM, Davis IC, Matalon S: Hyperoxia impairs antibacterial function of macrophages through effects on actin. Am J Respir Cell Mol Biol 2003, 28(4):443-450.
• [45]Cain H, Krauspe R, Kraus B: The cytoskeleton in activated and functionally disordered cells of the macrophage system. Pathol Res Pract 1982, 175(2–3):162-179.
• [46]Waterman-Storer CM, Salmon ED: Positive feedback interactions between microtubule and actin dynamics during cell motility. Curr Opin Cell Biol 1999, 11:61-67.