Effect of interferon-gamma on the 5-lipoxygenase pathway of rat lung macrophages.
In view of conflicting reports concerning the effect of macrophage activation on arachidonic acid metabolism, we examined the effect of the macrophage activator, interferon-gamma (IFN-gamma), on the 5-lipoxygenase pathway in rat lung macrophages. Rat lung macrophages were conditioned in the presence or absence of 10(2) U/ml IFN-gamma for 4 h before stimulation with 1 microM A23187 for 15 min or 100 micrograms/ml opsonized zymosan for 60 min at 37 degrees C as well as other stimuli. Lipoxygenase products in extracted cell supernatants were identified and analyzed by high-pressure liquid chromatography and ultraviolet spectroscopy. The predominant lipoxygenase products included leukotriene (LT) B4, LTC4, and 5-hydroxyeicosatetraenoic acid (5-HETE). These products were not qualitatively altered by conditioning with IFN-gamma. However, 5-lipoxygenase pathway activity, as measured by LTB4 release, was maximally increased 2-fold after conditioning with IFN-gamma and stimulating with either A23187 or opsonized zymosan. IFN-gamma-conditioned macrophages, stimulated with A23187, released greater quantities of lipoxygenase products in comparison with control cells (307.6 +/- 13.3 versus 167.6 +/- 3.9 pmol LTB4/10(6) cells) (mean +/- SEM) (P less than 0.05). Similar results were obtained with the less potent stimulus, opsonized zymosan. IFN-gamma had no direct stimulatory effect on the 5-lipoxygenase pathway. No effect was observed with a variety of other stimuli with or without IFN-gamma conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)
Meslier
N
N
Cardiovascular Research Institute, University of California, San Francisco.
Aldrich
A J
AJ
Bigby
T D
TD
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins
D001095:Arachidonic Acids; D011994:Recombinant Proteins; D007371:Interferon-gamma; D001094:Arachidonate 5-Lipoxygenase