Reduction of neutrophil-mediated injury to pulmonary endothelial cells by dapsone.
The presence of activated neutrophils in the alveolar structures is thought to contribute to parenchymal cell injury in various acute and chronic lung disorders. This study indicates that dapsone (30 micrograms/ml), an agent with anti-inflammatory properties, can significantly reduce neutrophil-mediated injury to 51Cr-labeled bovine pulmonary artery endothelial (BPAE) cells with a reduction in the injury (expressed as a cytotoxic index) from 65 +/- 3 to 33 +/- 3 (p less than 0.001). Dapsone was unable to protect 51Cr-labeled BPAE cells injured by the chemical generation of superoxide, hydrogen peroxide, or neutrophil-derived, myeloperoxidase-dependent hypohalite ion. In contrast, dapsone significantly inhibited the respiratory burst of the neutrophil, with a reduction in the generation of superoxide, hydrogen peroxide, and conversion of nitroblue tetrazolium to formazan (p less than 0.01, all comparisons). Thus, dapsone appears to protect lung parenchymal cells such as endothelial cells from neutrophil-mediated injury by directly inhibiting the respiratory burst of the neutrophil, with a consequent diminution in the generation of toxic, oxygen-derived radicals.
Martin
W J
WJ
Kachel
D L
DL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003622:Dapsone / Q000494:pharmacology*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D055370:Lung Injury; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013481:Superoxides / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D005609:Free Radicals; D013481:Superoxides; D003622:Dapsone; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate