Effects of phospholipase A2 and its hydrolytic products on alveolar epithelial permeability and elastase-induced emphysema.
To cause emphysema, proteases that are instilled into the air spaces must first be transported across the alveolar epithelium, a barrier that is normally quite impermeable to macromolecules. It was postulated that phospholipase A2 (PLA2) exposure would potentiate porcine pancreatic elastase (PPE)-induced epithelial solute permeability in a manner similar to that which was previously shown with lysophosphatidylcholine (lysoPC), a naturally occurring, membrane-perturbing agent that is formed principally through the hydrolysis of phosphatidylcholine by PLA2. Groups of hamsters were given intratracheal injections of PLA2 (0.3 units) or one of the expected hydrolytic products of PLA2 in equimolar concentrations, lysoPC (135 micrograms), arachidonic acid (AA) (100 micrograms), or palmitic acid (PA) (70 micrograms) with or without PPE (4 units). Epithelial permeability surface area products (PS) of the alveolar epithelium to [14C]sucrose and 125I-labeled neutral dextran (MW, 70,000) were measured in isolated perfused lungs 30 min after instillation, and emphysema severity was assessed at 3 wk by pressure-volume relationships and by mean linear intercepts. Additionally, the effects of lysoPC, PA, and AA on the functions of PPE and alpha 1-antiprotease (alpha 1 PI) in vitro were evaluated. Sucrose and dextran 70 PS differed significantly from controls only in those groups of hamsters that received PLA2 of lysoPC (p less than 0.05). LysoPC and PLA2 also potentiated the severity of PPE-induced emphysema to a similar degree (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Rice
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KL
Pulmonary Section, Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Duane
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PG
Niewoehner
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DE
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D006224:Cricetinae; D004347:Drug Interactions; D004549:Elastin / Q000494:pharmacology; D004646:Emphysema / Q000139:chemically induced / Q000503:physiopathology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006868:Hydrolysis; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008647:Mesocricetus; D010196:Pancreatic Elastase / Q000494:pharmacology; D010539:Permeability; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism / Q000494:pharmacology*; D054467:Phospholipases A2; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D008244:Lysophosphatidylcholines; D000515:alpha 1-Antitrypsin; D004549:Elastin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010196:Pancreatic Elastase