LUNG PARENCHYMAL INJURY INDUCED BY BLEOMYCIN

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Abstract
Bleomycin, a chemotherapeutic agent used to treat various malignancies, is thought to directly injure lung tissue. Granulocytes, which can also injure lung tissue, are found in large numbers in the initial stages of bleomycin-induced lung injury. An in vitro method, using 3H-uridine-labeled rat lung explants as the target tissue, was used to determine whether bleomycin could directly injure lung tissue. Bleomycin itself injured the explants in a dose-dependent manner. Supernatants of explants exposed to bleomycin exhibited chemotactic activity for granulocytes. The bleomycin-exposed tissues, but not their supernatants, induced granulocytes to produce superoxide anion. These studies demonstrated that bleomycin can directly injure lung tissue at doses approaching peak serum levels in humans, and that granulocytes may be attracted to the lung by a chemotactic factor released by lung tissue injured by bleomycin. These studies suggested that granulocytes may play a significant role in bleomycin-induced lung injury.