Injurious effects of lysophosphatidylcholine on barrier properties of alveolar epithelium.
We studied the effects of lysophosphatidylcholine (lysoPC) on the barrier properties and the morphology of the alveolar-capillary membrane in isolated, fluid-filled hamster lungs continuously perfused. When instilled into the airspace at initial concentrations of 8-128 micrograms/ml, lysoPC causes dose-dependent increases in the permeability-surface area product of the alveolar epithelium for small (14C-sucrose, 342) and large (125I-neutral dextran, 70,000) solutes, with maximal values for each solute approximately 15 times control. Rapid whole-lung weight gains are caused by 128 micrograms lysoPC per milliliter, but each of the lower concentrations has no effect on net lung water balance. Electron-microscopic studies demonstrate that type I pneumonocytes are the lung cells most susceptible to lysoPC exposure, with cell swelling being the most prominent feature from low-dose exposure with more severe disruptive changes at the highest concentration tested. The effects of lysoPC are relatively specific, as several structurally related lipids have little or no effect at equivalent concentrations. Instillation of phospholipase A2 causes functional changes similar to those seen with lysoPC, presumably by generation of lysoPC from endogenous phospholipids. Studies employing a 14C-radiolabeled compound show that instilled lysoPC rapidly partitions into the lung lipid fraction where a major portion of the acyl group becomes incorporated into phosphatidylcholine. The amount of instilled lysoPC required to produce functional and morphological effects comprises only a few percent of total lung phospholipids. Since lysoPC is a normal component of lung phospholipids, severe lung dysfunction might result from minor abnormalities in the formation or degradation of this compound.
Niewoehner
D E
DE
Veterans Administration Medical Center, Minneapolis, Minnesota.
Rice
K
K
Sinha
A A
AA
Wangensteen
D
D
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D005260:Female; D006735:Horseradish Peroxidase; D008055:Lipids / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature
D008055:Lipids; D008244:Lysophosphatidylcholines; D006735:Horseradish Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2