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 have been shown to modulate inflammatory responses in vivo and neutrophil and platelet function in vitro we investigated the effects of
prostaglandin E1 (
PGE1) on
ANTU -induced
lung injury. 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, subcutaneously) administered 1 hour prior to
ANTU treatment (1 mg/kg, intraperitoneally) resulted in a 164% increase (p less than 0.001) in
pleural effusion formation and a 42% increase (p less than 0.02) in
wet lung weight at 4 hours 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-prostaglandin F2 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 approximately 50% decreased aggregation response to
adenosine diphosphate. 15-M-PGE1 (1 mg/kg) treatment combined with platelet depletion resulted in a 1.7-fold increase (p less than 0.01) in
pleural effusions in
ANTU -treated (1 mg/kg) animals compared with platelet depletion alone. These studies indicate that 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.