Mechanisms and mediators in coal dust induced toxicity: A review

Chronic inhalation of coal dust can clause several lung disorders, includin g simple coal workers pneumoconiosis (CWP), progressive massive fibrosis (P MF), chronic bronchitis, lung function loss, and emphysema. This review foc uses on the cellular actions and interactions of key inflammatory cells and target cells in coal dust toxicity and related lung disorders, i.e. macrop hages and neutrophils, epithelial cells, and fibroblasts. Factors released from or affecting these cells are outlined in separate sections, i.e. (1) r eactive oxygen species (ROS) and related antioxidant protection mechanisms, and (2) cytokines, growth factors and related proteins. Furthermore, (3) c omponents of the extracellular matrix (ECM), including the modifying role o f 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-cellula r and cellular sources of ROS in the lung, and may be significantly involve d in the damage of lung target cells as well as important macromolecules in cluding 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 (macrophag e) production of various factors with potential capacity to modulate lung c ells and/or extracellular matrix, including O-2( ).(-), H2O2, and NO, fibro blast chemoattractants (e.g. Transforming Growth Factor-beta (TGF beta), PD GF, and fibronectin) and a number of factors that have been shown to stimul ate and/or inhibit fibroblast growth or collagen production such as (TNF al pha, TGF beta, PDGF, Insulin Like Growth Factor, and Prostaglandin-E-2). Fu rther studies are needed to clarify the ill vivo kinetics and relative impa ct of these factors. (C) 1999 British Occupational Hygiene Society. Publish ed by Elsevier Science Ltd.