Pleural mesothelial cells mediate inflammatory and profibrotic responses in talc-induced pleurodesis.
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 mug/cm(2)) 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-beta(1) (TGF-beta(1)) 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-beta(1) 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.
Acencio
Milena Marques P
MM
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. milena.acencio@incor.usp.br
Vargas
Francisco S
FS
Marchi
Evaldo
E
Carnevale
Gabriela G
GG
Teixeira
Lisete R
LR
Antonangelo
Leila
L
Broaddus
V Courtney
VC
D000818:Animals; D051520:Antiperspirants / Q000633:toxicity; D017209:Apoptosis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D010994:Pleura / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D018700:Pleurodesis / Q000009:adverse effects* / Q000379:methods; D011817:Rabbits; D013627:Talc / Q000008:administration & dosage / Q000633:toxicity*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051520:Antiperspirants; D016209:Interleukin-8; D016211:Transforming Growth Factor alpha; D042461:Vascular Endothelial Growth Factor A; D013627:Talc