Effects of PM10 in human peripheral blood monocytes and J774 macrophages.

Brown, David M, Donaldson, Ken and Stone, Vicki (2004) Effects of PM10 in human peripheral blood monocytes and J774 macrophages. Respiratory Research, 5 (1). p. 29.

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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.

Item Type: Article
Electronic ISSN: 1465-9921
Uncontrolled Keywords: Macrophage; Nanoparticle; Cytokine; Cytoskeleton; PM10
University Divisions/Research Centres: Faculty of Health, Life & Social Sciences > School of Life Sciences
Dewey Decimal Subjects: 600 Technology > 610 Medicine & health > 612 Human physiology
600 Technology > 610 Medicine & health > 611 Human anatomy, cytology & histology
600 Technology > 610 Medicine & health > 614 Incidence & prevention of disease
Library of Congress Subjects: Q Science > QP Physiology
Q Science > QM Human anatomy
Item ID: 1640
Depositing User: RAE Import
Date Deposited: 20 Jun 2008 14:11
Last Modified: 11 Feb 2011 13:58

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