Abstract
Intrapleural talc is used to produce pleurodesis in malignant pleural effusions. Prior in vivo studies have documented an acute inflammatory response to talc in the pleural space but the cellular source of cytokines has not been identified. The aim of this study was to investigate the acute response of rabbit pleural mesothelial cells challenged with talc used for pleurodesis and compare it to prior studies of the response to talc in the rabbit pleural space. Cultured rabbit pleural mesothelial cells (PMC) were exposed to talc (25 μg/cm2) for 6, 24, or 48 h and assessed for viability, necrosis, and apoptosis by flow cytometry, Trypan Blue exclusion, and immunocytochemistry, and for the production of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGF-β1) by ELISA. More than 50% of the PMC remained viable 48 h after talc stimulation. The PMC that were nonviable were identified as either apoptotic or necrotic, with roughly 20% in each category over the 48 h. At 6 h, the IL-8, VEGF, and TGF-β1 levels produced by talc-exposed PMC increased significantly and remained elevated for up to 48 h. These cytokine levels rose at similar times and at the same or higher levels than have been measured in the rabbit pleural space in prior studies. We report that viable, talc-exposed, pleural mesothelial cells may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.
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Light RW (2001) Pleural diseases, 4th ed. Philadelphia, PA: Lippincot Williams & Wilkins
Hausheer FH, Yarbro JW (1985) Diagnosis and treatment of malignant pleural effusions. Semin Oncol 12:54–75
Hartman DL, Gaither JM, Kesler KA, Mylet DM, Brown JW, Mathur PN (1992) Thoracoscopic talc pleurodesis with standard chest tube using tetracycline and bleomycin for control of malignant pleural effusions. J Thorac Cardiovasc Dis 105:743–748
Hartman DL, Antony VB (1993) Pleurodesis: now what should we use? J Respir Dis 14:347–351
Sahn SA, Good JT (1981) The effect of common sclerosing agents on the rabbit pleural space. Am Rev Respir Dis 124:65–67
Boylan AM, Ruegg C, Kim KJ, Hebert CA, Hoeffel JM, Pytela R, Sheppard D, Goldstein IM, Broaddus VC (1992) Evidence of a role for mesothelial cell-derived interleukin-8 in the pathogenesis of asbestos induced pleurisy in rabbits. J Clin Invest 89:1257–1267
Goodman RB, Wood RG, Martin TR, Hanson-Painton O, Kinasewitz GT (1992) Cytokine-stimulated human mesothelial cells produce chemotactic activity for neutrophils including NAP-1/IL-8. J Immunol 148:457–465
Lee GYC, Melkerneker D, Thompson PJ, Light RW, Lane KB (2002) Transforming growth factor beta induces vascular endothelial growth factor elaboration from pleural mesothelial cells in vivo and in vitro. Am J Respir Crit Care Med 165:88–94
Anthony VB, Nasreen N, Mohammed KA, Sriram PS, Frank W, Schoenfeld N, Loddenkemper R (2004) Talc pleurodesis: basic fibroblast growth factor mediates pleural fibrosis. Chest 126:1522–1528
Marchi E, Vargas FS, Acencio MMP, Antonangelo L, Genofre EH, Teixeira LR (2006) Evidence that mesothelial cells regulate the acute inflammatory response in talc pleurodesis. Eur Respir J 28:929–932
Genofre EH, Vargas FS, Antonangelo L, Teixeira LR, Vaz MA, Marchi E, Capelozzi VL (2005) Ultrastructural acute features of active remodeling after chemical pleurodesis induced by silver nitrate or talc. Lung 183:197–207
Marchi E, Liu W, Broaddus VC (2000) Mesothelial cell apoptosis is confirmed in vivo by morphological change in cytokeratin distribution. Am J Physiol Lung Cell Mol Physiol 278:L528–L535
Marchi E, Vargas FS, Acencio MMP, Antonangelo L, Teixeira LR, Genofre E, Light RW (2004) Talc and silver nitrate induce systemic inflammatory effects during the acute phase of experimental pleurodesis in rabbits. Chest 125:2268–2277
Antony VB, Owen CL, Hadley KJ (1989) Pleural mesothelial cells stimulated by asbestos release chemotactic activity for neutrophils in vitro. Am Rev Respir Dis 139:199–206
Ferrara N (1999) Molecular and biological properties of vascular endothelial growth factor. J Mol Med 77:527–543
Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor and its receptors. FASEB J 13:9–22
Light RW, Cheng DS, Lee YCG, Rogers J, Davidson J, Lane KB (2000) A single intrapleural injection of transforming growth factor beta-2 produces an excellent pleurodesis in rabbits. Am J Respir Crit Care Med 162:98–104
Mutsaers SE, Wilkosz S (2007) Structure and function of mesothelial cells. Cancer Treat Res 134:1–19
Hage CA, Mohammed KA, Antony VB (2004) Pathogenesis of pleural infection. Respirology 9:12–15
Mutsaers SE, Kalomenidis I, Wilson NA, Lee YCG (2007) Growth factors in pleural fibrosis. Curr Opin Pulm Med 12:251–258
Staub NC, Wiener-Kronish JP, Albertine KH (1985) Transport through the pleura: physiology of normal liquid and solute exchange in the pleural space. In: The Pleura in Health and Disease. New York: Dekker, vol 30, pp 169–193
Acknowledgments
The authors thank Karla S. Sakuma and Carlos S. R. Silva for their valuable collaboration in this study. Supported by FAPESP 05/55599-8
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Acencio, M.M.P., Vargas, F.S., Marchi, E. et al. Pleural Mesothelial Cells Mediate Inflammatory and Profibrotic Responses in Talc-induced Pleurodesis. Lung 185, 343–348 (2007). https://doi.org/10.1007/s00408-007-9041-y
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DOI: https://doi.org/10.1007/s00408-007-9041-y