POLYAMINES, POLYMORPHS AND EXPERIMENTAL RESPIRATORY DISTRESS SYNDROME

Abstract

The polyamines (PAs) spermine (SPM) and SPM plus spermidine (SPD) produce lesions in B alb C mice as found in Adult Respiratory Distress Syndrome (ARDS). Endocapillary margination of polymorphs (PMNs) was seen 30 min. after i.p. SPM (75 mg/kg bw). At 60 min. endothelial cell vacuolization, RBC engorgement and hemorrhage were observed. Loss of interdigitating cell boundaries suggested edema formation. Seven day PA exposure (SPM 15 mg/kg/d plus SPD 30 mg/kg/d, i.p.) produced severe damage. Leukergy, band-form margination, microatalectasis and hyperplastic type II epithelial cell desquamation in suffused alveoli were noted. Resident PMN swelling included both nuclear chromatin reorganization and cytoplasmic liquifaction. Dissolution of organelles preceded plasma and nuclear membrane lysis. Residual moth-eaten stroma suggested widespread proteolysis. SPM (15 mg/kg/d, i.p.) for 21 days induced fibroblast and type II cell proliferation and fibrotic replacement of parenchyma. Infection, surgery, irradiation, cytoxic drug and collagen-vascular disorders cause increased blood and urinary PA levels and are initial clinical events in ARDS. In our model PAs promote a sustained PMN-endothelial cell membrane association and interstitial edema as the earliest morphological events in the ARDS sequence. This is provisionally attributed to several possible concurrent reactions including poly-electrolyte bridging, endocytotic receptor down-regulation and/or structural surface point charge alteration.