Release of prostaglandin E2 and leukotriene B4 by alveolar macrophages from patients with sarcoidosis.
BACKGROUND
Mediators released by alveolar macrophages, as well as by T cells, play an important part in modulating local immune processes in sarcoidosis. Among alveolar macrophage secretory products, arachidonic acid metabolites are known to regulate inflammatory and immune reactions. It has been suggested that cyclo-oxygenase and lipoxygenase pathway metabolites of arachidonic acid modulate the evolution of the granulomatous inflammatory response in the lung differently.


METHODS
Alveolar macrophages recovered from the bronchoalveolar lavage (BAL) fluid of 32 patients with sarcoidosis in different states of disease activity and 10 normal subjects were evaluated for their ability to release prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). Alveolar macrophages were cultured in the presence or absence of opsonised zymosan (500 micrograms/ml), and PGE2 and LTB4 levels in the culture supernatants were determined by enzyme immunoassay (EIA).


RESULTS
Stimulated alveolar macrophages from patients with active sarcoidosis released higher LTB4 levels than those from normal subjects, but no differences in PGE2 release were observed between the two groups. The time course of LTB4 release by activated alveolar macrophages showed that normal cells produced similar levels of the hydroxyacid during the early and late times of culture while LTB4 release by activated cells from patients with sarcoidosis increased markedly after 60 minutes of culture, remaining elevated until 24 hours. Indomethacin (3 x 10(6) M) caused the expected inhibition of PGE2 formation without affecting LTB4 release.


CONCLUSIONS
These results suggest that alveolar macrophages from the BAL fluid of patients with active sarcoidosis are primed to release LTB4, which may contribute to the locally heightened immune response.
De Rose
V
V
Department of Clinical and Biological Sciences, University of Turin, Italy.
Trentin
L
L
Crivellari
M T
MT
Cipriani
A
A
Gialdroni Grassi
G
G
Pozzi
E
E
Folco
G
G
Semenzato
G
G
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism*; D018655:Lymphocyte Count; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism*; D012507:Sarcoidosis / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D007975:Leukotriene B4; D015054:Zymosan; D007213:Indomethacin