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ABSTRACT: BAL in patients with ARDS provides material containing the soluble and cellular constituents of the alveolar compartment, and hence is a useful tool for the study of the pathogenesis of ARDS. The technique is imperfect as it is prone to problems of data acquisition and interpretation. However, it is lung-specific and may be used in serial studies of patients over the course of their disease. A large amount of evidence is rapidly being accumulated which documents the presence of effectors of inflammation in the BAL fluids of patients with ARDS. Confirmation of the importance of such mediators, pathways, or cellular constituents of BAL fluid in establishing the pathogenesis of ARDS ultimately depends upon proof of the efficacy of specific clinical interventions which both arrest the activity of the effector and predictably alter the course of the disease.
Clinics in Chest Medicine 10/1985; 6(3):459-71. · 3.28 Impact Factor
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Clinics in Chest Medicine 10/1983; 4(3):359-75. · 3.28 Impact Factor
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ABSTRACT: It was hypothesized that IL-8, a neutrophil chemotaxin, contributes to the influx of neutrophils into the pleural cavity of patients with pleural effusions. Pleural fluids were collected from 57 patients including 13 with effusions due to congestive heart failure, 28 with pleural involvement by carcinoma, 5 with empyema, 4 with parapneumonic effusions complicating bacterial pneumonia, 3 with hemothorax, 3 with tuberculosis, and 1 with rheumatoid arthritis. All exudate groups had significantly higher IL-8 concentrations than the CHF group (p < .001). In 18 of the exudate fluids, the concentrations of IL-8 was equal to or in excess of the optimal concentration of IL-8 which causes neutrophil chemotaxis in vitro. Between 20 and 90% of the chemotactic activity in the fluids was removed by absorbing the IL-8 with an IL-8 affinity column. These data showed that IL-8 is a major chemotaxin in the fluid. The percentage of neutrophils in the fluids was not correlated with the IL-8 concentration. Although TNF alpha, a potent stimulator of IL-8 production, is present in some pleural effusions, no correlation was found between the concentrations of IL-8 and TNF alpha in the fluids. The data suggest that IL-8 contributes to the neutrophil influx into the pleural space of patients with pleural exudates in conjunction with other chemoattractants. It is unlikely that TNF alpha is the sole stimulus for the IL-8 production in pleural disease states.
Experimental Lung Research 19(5):589-601. · 1.22 Impact Factor
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ABSTRACT: The mesothelium contains both procoagulant and fibrinolytic activities. An imbalance between these activities could account for the abnormal fibrin turnover and pleural fibrin deposition that is characteristic of pleural inflammation. Procoagulant activity of human pleural mesothelial cells (HPMC) is in part due to tissue factor, and the prothrombinase complex can also assemble at the HPMC surface. HPMC express tissue plasminogen activator (tPA) but no detectable fibrinolytic activity in a fibrin plate assay. Inhibition of HPMC fibrinolytic activity is due, in part, to elaboration of plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) as well as antiplasmins. Synthesis of PAI-1 and PAI-2 is inhibited by actinomycin D and cyclohexamide. HPMC PAI-1 is increased by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), as is tPA release, while PAI-1 mRNA is unchanged and tPA mRNA is increased. PAI-2 release is induced by TNF-alpha and TGF-beta. Because they are a rich source of PAI-1 and PAI-2, HPMC may contribute to the high levels of these inhibitors in pleural exudates. Stimulation of HPMC by TNF-alpha or TGF-beta in vitro did not alter HPMC procoagulant activity nor the balance of elevated PAI and antiplasmins relative to PA, changes that collectively favor formation and persistence of pericellular fibrin.
Am J Respir Cell Mol Biol. 7(4):414-26.
