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1.
Am J Respir Crit Care Med ; 162(3 Pt 1): 958-65, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10988113

ABSTRACT

Previous studies on symptomatic coal miners have shown that alveolar macrophages, recovered by bronchoalveolar lavage (BAL), release excessive amounts of reactive oxygen species (ROS) and inflammatory cytokines. It has been proposed that these secretions may mediate cell injury and initiate the disease process. We hypothesized that acellular bronchoalveolar lavage fluid (BALF) indices in coal miners chronically exposed to coal dust may reflect the status of important homeostatic modulations in the lung that lead to the development of coal workers' pneumoconiosis (CWP). To test this hypothesis, we measured inflammatory status, oxidant burden, antioxidant defenses, cytokines, growth factors, fibronectin, and alpha(1)-antitrypsin (alpha(1)-AT) in the BALF of healthy never-smoker control subjects, never-smoker underground coal miners with negative radiographs (ILO 0/0-1/0), and two miners with moderate changes in the chest radiographs (ILO 2/2). Interestingly, indices of injury and inflammation increased with the progression of disease in coal miners. Antioxidant enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase, showed a 19-fold, 22-fold, and 6-fold increase above control, respectively, in coal miners with category 2/2 CWP. Significant increases in the secretion of IL-1, IL-6, TNF-alpha, TGF-beta, fibronectin, and alpha(1)-AT also were evident in coal miners with disease. This up-regulation of antioxidant defenses and cytokines was not evident in coal miners in the absence of clinically evident radiographic disease. In addition, the concentration of lipid peroxidation by products in the BALF of coal miners without evidence of radiographic disease showed a moderate 3-fold increase, whereas, in coal miners with category 2/2 CWP it showed a 59-fold increase compared to control subjects. These results are in good agreement with our hypothesis that development of CWP and its progression may be correlated with an oxidative stress and up-regulation of cytokines and mediators of growth.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Cytokines/metabolism , Inflammation Mediators/metabolism , Pneumoconiosis/diagnostic imaging , Reactive Oxygen Species/metabolism , Adult , Humans , Lipid Peroxidation/physiology , Lung/physiopathology , Male , Middle Aged , Oxidative Stress/physiology , Pneumoconiosis/physiopathology , Predictive Value of Tests , Radiography
2.
Environ Health Perspect ; 106 Suppl 5: 1165-9, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9788892

ABSTRACT

In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. In vitro exposure of AM to silica does not stimulate .NO production or enhance iNOS message. However, treatment of naive AM with conditioned media from BALC harvested from silica-exposed rats does increase iNOS message and .NO production by these AM. The potency of this conditioned medium is dependent on interaction between AM and PMN. In the rat model, a relationship exists between the ability of various dusts to cause PMN recruitment or protein leakage into the alveolar space and the induction of iNOS message in BALC, i.e., silica > coal mine dust > carbonyl iron > titanium dioxide. Similarly, a comparison of BALC from a healthy volunteer, a silica-exposed coal miner with a normal chest radiograph, and a silica-exposed coal miner with an abnormal chest radiograph shows a correlation between pathology and both the level of iNOS message in BALC and the magnitude of .NO-dependent CL from AM. These data suggest that .NO may play a role in silicosis and that human pulmonary phagocytes exhibit enhanced .NO production in response to an inflammatory insult.


Subject(s)
Lung/drug effects , Lung/metabolism , Nitric Oxide/biosynthesis , Silicon Dioxide/toxicity , Animals , Bronchoalveolar Lavage Fluid/cytology , Coal Mining , Humans , In Vitro Techniques , Luminescent Measurements , Lung/cytology , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/metabolism , Male , Neutrophils/drug effects , Neutrophils/metabolism , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Occupational Exposure , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Inbred F344 , Rats, Sprague-Dawley , Up-Regulation/drug effects
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