Induction of alveolar epithelial injury by phospholipase A2.
Severe damage to the alveolar type I epithelial cell is a characteristic morphological feature of lung injury due to numerous cases. It is postulated that excess phospholipase A2 (PLA2) activity might be responsible for these changes, as one of the naturally occurring products of this enzyme, lysophosphatidylcholine (lysoPC) has been shown to cause selective injury to the type I pneumonocyte when it is instilled into the lower air spaces of the lung. To further investigate this potential mechanism of type I epithelial cell toxicity, we have measured the epithelial permeability-surface area product (PS) for [14C]sucrose as well as whole-lung lysoPC content at several times after instilling PLA2 (Naja naja venom) into either the air spaces or the perfusate of an isolated hamster lung preparation. As a molar percentage of total phospholipids, the normal hamster lung contains approximately 1.5% lysoPC, and this value is not affected by fluid filling of the air spaces or perfusion of the excised lung for periods up to 90 min. When 0.15 U/ml PLA2 is instilled into the air spaces, lung lysoPC content increases to approximately 2.5% and there are barely detectable increases in [14C]sucrose PS. With air space PLA2 concentrations of 0.30 U/ml, lysoPC content increases to between 4 and 5%, [14C]sucrose PS increases by greater than a factor of 10, and flooding of the alveolar spaces occur. Ultrastructural studies of similarly treated lungs show widespread but selective damage to the type I epithelial cells. These same biochemical and functional changes are not seen when the same concentrations of PLA2 are added to the lung perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)
Niewoehner
D E
DE
Veterans Administration Medical Center, Minneapolis, Minnesota.
Rice
K
K
Duane
P
P
Sinha
A A
AA
Gebhard
R
R
Wangensteen
D
D
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D006224:Cricetinae; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006868:Hydrolysis; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008647:Mesocricetus; D008854:Microscopy, Electron; D010477:Perfusion; D010539:Permeability; D010713:Phosphatidylcholines / Q000378:metabolism; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000473:pathology
D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010743:Phospholipids; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2