Prostaglandin and leukotriene production by alveolar type II cells in vitro.
Alveolar type II cells were isolated from adult rats, cultured for 22 h, and individual eicosanoids in the media from unstimulated and stimulated cells were quantified by immunoassay. Stimulation with the calcium ionophore A23187 significantly increased the media levels of prostaglandins (prostaglandin and 6-keto-prostaglandin F1 alpha greater than thromboxane B2). In contrast to previous reports, increased media levels of leukotrienes were also recovered from cells incubated with A23187, but only for cells in culture for less than or equal to 24 h. The production of leukotriene C4 was confirmed by a combination of high-performance liquid chromatography and spectrophotometric analysis. The profile of eicosanoids produced by cultures of alveolar type II cells was distinctly different than that of similarly cultured alveolar macrophages. Finally, stimulation of alveolar type II cell cultures with either a phorbol ester or phospholipase C increased media prostaglandin levels but failed to increase leukotriene levels. We conclude that primary cultures of alveolar type II cells are capable of the de novo metabolism of arachidonic acid to both cyclooxygenase and lipoxygenase products and that the production of leukotrienes is dependent on both time in culture and agonist. Thus alveolar type II cells are a potential source for the production of these eicosanoids in vivo, and the particular lipid mediators produced may vary depending on the pathophysiologic stimulus.
Cott
G R
GR
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
Westcott
J Y
JY
Voelkel
N F
NF
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D015777:Eicosanoids / Q000096:biosynthesis*; D007700:Kinetics; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000302:isolation & purification; D015289:Leukotrienes / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015777:Eicosanoids; D015289:Leukotrienes; D011453:Prostaglandins; D007975:Leukotriene B4; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate