Cytochrome P-450-dependent metabolism in alveolar type II epithelial cells: modulation by platelet-activating factor.
Platelet-activating factor (PAF), an ether lipid mediator released from activated pulmonary phagocytes, was evaluated for its ability to affect cytochrome P-450-dependent activities in isolated rat alveolar type II cells. The data indicate that at non-toxic doses, PAF caused an increase in beta-naphthoflavone (BNF) inducible/alpha-naphthoflavone (ANF) sensitive ethoxyphenoxazone deethylase (EtOPx'ase) activity. At high concentrations of PAF, inhibition of both EtOPx'ase and metyrapone (MP) sensitive benzyloxyphenoxazone debenzylase (BzOPx'ase) activities and aggregation of type II cells were observed. The PAF analogs, lyso-PAF and enantio-PAF, exhibited actions similar to those observed with PAF. PAF-induced enhancement of EtOPx'ase activity required the presence of intact cells, whereas at high PAF concentrations decreased enzyme activities were observed in both intact cell and sonicated cell preparations. The data thus suggest that xenobiotic metabolism in alveolar type II cells can be modified by an inflammatory mediator, such as PAF, produced by alveolar phagocytes.
Rabovsky
J
J
National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies, Morgantown, WV 26505.
Pailes
W H
WH
Judy
D J
DJ
Castranova
V
V
D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D010972:Platelet Activating Factor / Q000737:chemistry / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D010972:Platelet Activating Factor; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1