POTENTIATION OF ALPHA-NAPHTHYL THIOUREA-INDUCED LUNG INJURY BY PROSTAGLANDIN-E1 AND PLATELET DEPLETION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 50  (6) , 703-710
Abstract
.alpha.-Naphthyl thiourea (ANTU) produces pulmonary endothelial injury, pulmonary edema and pleural effusions in rats in a dose-dependent manner. Since prostaglandins of the E series modulate inflammatory responses in vivo and neutrophil and platelet function in vitro the effects of prostaglandin E1 (PGE1) on ANTU-induced lung injury were investigated. Systemic administration of 15-(S)-15-methyl-PGE1 (15-M-PGE1), a stable analog of PGE1, potentiated lung injury induced by ANTU in a dose- and time-dependent manner. 15-M-PGE1 (1 mg/kg, s.c.) administered 1 h prior to ANTU treatment (1 mg/kg, i.p.) resulted in a 164% increase (P < 0.001) in pleural effusion formation and a 42% increase (P < 0.02) in wet lung weight at 4 h after ANTU administration. This was associated with increased pulmonary endothelial cell blebbing and gap formation with a decrease in the number of platelet thrombi in 15-M-PGE1-treated animals compared with controls. 15-(S)-15-methyl-PGF2.alpha. was less effective than 15-M-PGE1 in potentiating ANTU-induced lung injury. Platelet depletion, but not neutrophil depletion, also potentiated ANTU-induced lung injury, suggesting a protective role for platelets. Platelets isolated from 15-M-PGE1-treated animals demonstrated an .apprx. 50% decreased aggregation response to ADP. 15-M-PGE1 (1 mg/kg) treatment combined with platelet depletion resulted in a 1.7-fold increase (P < 0.01) in pleural effusions in ANTU-treated (1 mg/kg) animals compared with platelet depletion alone. Systemic treatment of rats with 15-M-PGE1 will potentiate ANTU-induced lung injury. This injury may be in part secondary to the ability of 15-M-PGE1 to inhibit platelet function. However, platelet depletion studies suggest that 15-M-PGE1 has additional effects, possibly on endothelial cells and/or vascular smooth muscle cells that contribute to the potentiation of ANTU-induced lung injury.

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