Neutrophils potentiate platinum-mediated injury to human ciliated epithelium in vitro.
Exposure to platinum salts, such as may occur in the platinum refining industry, can be associated with the development of airway disorders such as asthma. However, there have been no studies investigating the direct effects of platinum salts on human ciliated epithelium. We have investigated the effects of platinic chloride on human ciliated epithelium, obtained by brushing the inferior nasal turbinate of healthy human volunteers. Ciliary beat frequency was measured using a phototransistor technique, and damage to the structural integrity of the epithelium was measured using a visual scoring index. Platinic chloride at concentrations between 0.25 and 25 microM caused a dose-dependent slowing of ciliary beating and damage to the structural integrity of the epithelium. These direct injurious effects were not affected by catalase, but were almost completely attenuated by preincubation of the epithelium with cysteine. The effects of platinic chloride on ciliary beating and structural integrity were enhanced by the presence of neutrophils and were partially attenuated by preincubation of the epithelial strips with catalase, suggesting that the direct effects of the metal were enhanced in this experimental system by reactive oxidants produced by activated neutrophils. This study documents that platinum salts have an injurious effect on human ciliated epithelium in vitro. If such effects also occur in vivo they may play a role, at least partly, in the pathogenesis of airway disorders that may manifest in exposed workers.
Feldman
Charles
C
Division of Pulmonology, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa. feldmanc@medicine.wits.ac.za
Theron
Annette
A
Anderson
Ronald
R
D000166:Acridines; D000328:Adult; D002374:Catalase / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects* / Q000378:metabolism; D002925:Ciliary Motility Disorders / Q000139:chemically induced / Q000517:prevention & control; D003545:Cysteine / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004848:Epithelium / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods; D009297:Nasal Mucosa / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017671:Platinum Compounds / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D013482:Superoxide Dismutase / Q000378:metabolism
D000166:Acridines; D017671:Platinum Compounds; C030173:platinum chloride; C033472:10,10'-dimethyl-9,9'-biacridinium; D002374:Catalase; D013482:Superoxide Dismutase; D003545:Cysteine