Mechanisms and mediators in coal dust induced toxicity: a review.
Chronic inhalation of coal dust can cause several lung disorders, including simple coal workers pneumoconiosis (CWP), progressive massive fibrosis (PMF), chronic bronchitis, lung function loss, and emphysema. This review focuses on the cellular actions and interactions of key inflammatory cells and target cells in coal dust toxicity and related lung disorders, i.e. macrophages and neutrophils, epithelial cells, and fibroblasts. Factors released from or affecting these cells are outlined in separate sections, i.e. (1) reactive oxygen species (ROS) and related antioxidant protection mechanisms, and (2) cytokines, growth factors and related proteins. Furthermore, (3) components of the extracellular matrix (ECM), including the modifying role of ROS, cytokines, proteases and antiproteases are discussed in relation to tissue damage and remodelling in the respiratory tract. It is recognised that inhaled coal dust particles are important non-cellular and cellular sources of ROS in the lung, and may be significantly involved in the damage of lung target cells as well as important macromolecules including alpha-1-antitrypsin and DNA. In vitro and in vivo studies with coal dusts showed the up-regulation of important leukocyte recruiting factors, e.g. Leukotriene-B4 (LTB4), Platelet Derived Growth Factor (PDGF), Monocyte Chemotactic Protein-1 (MCP-1), and Tumor Necrosis Factor-alpha (TNF alpha), as well as the neutrophil adhesion factor Intercellular Adhesion Molecule-1 (ICAM-1). Coal dust particles are also known to stimulate the (macrophage) production of various factors with potential capacity to modulate lung cells and/or extracellular matrix, including O2-., H2O2, and NO, fibroblast chemoattractants (e.g. Transforming Growth Factor-beta (TGF beta), PDGF, and fibronectin) and a number of factors that have been shown to stimulate and/or inhibit fibroblast growth or collagen production such as (TNF alpha, TGF beta, PDGF, Insulin Like Growth Factor, and Prostaglandin-E2). Further studies are needed to clarify the in vivo kinetics and relative impact of these factors.
Department of Biological Sciences, Napier University, Edinburgh, U.K. r.schins@napier.ac.uk
R P
RP
Schins
P J
PJ
Borm
D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003031:Coal / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D004391:Dust / Q000009:adverse effects*; D010450:Endopeptidases / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009784:Occupational Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016273:Occupational Exposure / Q000009:adverse effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D000395:Air Pollutants, Occupational; D000975:Antioxidants; D003031:Coal; D016207:Cytokines; D004391:Dust; D006133:Growth Substances; D017382:Reactive Oxygen Species; D010450:Endopeptidases