Metabolism of platelet-activating factor in isolated perfused rat lung.

Abstract

The administration of platelet-activating factor (PAF) into the airway system of the lung is known to cause profound effects, yet little is known about the metabolism of this active lipid mediator. 3H-Labeled PAF administered into the airway of isolated rat lungs was rapidly and extensively metabolized. The tissue retained 96% of the administered radiolabel while the perfusate contained 4%. Characterization of the tissue retained lipid indicated metabolism into lyso-PAF (3.3%), phosphatidylcholine (82.3%), neutral lipid (1.7%) and intact PAF (10.2%). Analysis of tissue phosphatidylcholine by mass spectrometric techniques revealed metabolism of PAF to 1-0-hexadecyl-2-arachidonoyl-GPC, which represented 20-23% of the administered radiolabeled hexadecyl-PAF. These findings support the hypothesis that a relationship between PAF and arachidonate metabolism exists at the intact organ level. Autoradiographic analysis of the cellular distribution of the radiolabeled PAF metabolites in the lung tissue indicated labeling of two cell types, the alveolar type II cell and the nonciliated bronchiolar epithelial cell (Clara cell).