Cellular Localization of Flavin-Containing Monooxygenase in Rabbit Lung

Abstract

A specific form of flavin monooxygenase has been identified in the lungs of a number of species. Distribution of the pulmonary flavin-containing monooxygenase (FMOp) is of interest because it oxidatively metabolizes a wide variety of nitrogen-, sulfur-, and phosphorous-containing xenobiotics, some of which form highly toxic reactive intermediates. We have identified the nonciliated bronchiolar epithelial (Clara) cell as the predominant location for this enzyme in rabbit lung. In addition, protein in ciliated, endothelial, type I, and type II cells and in tracheal lining layer reacted with antibodies to FMOp. In all these cell types antigen was found associated with cytoplasmic organelles, and in the Clara cell antigen was most concentrated in areas rich in smooth endoplasmic reticulum. Staining of ciliated surfaces was also observed at both the light and electron microscopy levels. Extracellular antigen was also apparent in tracheal lining layer smeared onto glass slides. We compared the location of the FMOp with that of two enzymes of the cytochrome P-450 monooxygenase system (studied here and elsewhere), cytochrome P450 IIB (P450 IIB), and NADPH cytochrome P450 reductase (reductase), and concluded that (1) FMOp is detected in all cells where P450 IIB and reductase are both present (Clara, type II, and ciliated); (2) FMOp and P450 IIB, but not reductase, are detected in endothelial cells; (3) P450 IIB alone is detected in the plasma membrane, cilia, and microvillae of ciliated cells and plasma membrane of endothelial cells; and (4) FMOp alone is detected in type I cells.