Effects of indomethacin and prostaglandin E1 on the production of fibronectin and lysozyme by monocyte-derived macrophages in vitro.
Fibronectin secreted by macrophages may contribute to the development of pulmonary fibrosis. Prostaglandins are important regulators of macrophage metabolism whose role in the regulation of fibronectin production is not known. In this study, we examined the effects of PGE1 and indomethacin on human monocyte-derived macrophages exposed to these agents in culture for 10 to 14 days. Indomethacin (10 micrograms/ml) reduced the ratio of supernatant fibronectin to adherent cell DNA by 32%, p < 0.01, and reduced lysozyme/DNA by 29%, p < 0.0001. Exogenous PGE1 (1 ng/ml) did not affect fibronectin, but increased lysozyme/DNA by 27%, p < 0.01. In additional experiments, supernatant fibronectin and total protein synthesized in the presence of 3H-leucine were measured. Indomethacin (10 micrograms/ml) had no effect on total supernatant protein radioactivity, but reduced fibronectin/DNA by 33%, p < 0.001, and reduced fibronectin/total protein by 19%, p < 0.01. Since indomethacin increases macrophage secretion of plasminogen activator and interleukin-1, these experiments add to the evidence that specific secretory products of macrophages are regulated independently. We conclude that indomethacin at 10 micrograms/ml decreases the production of fibronectin and lysozyme by monocyte-derived macrophages. The modest size of the effect, and its absence at lower doses of indomethacin, indicate that prostaglandins are unlikely to have a major role in the regulation of macrophage production of fibronectin.
Smith
J B
JB
Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia.
Hassan
N F
NF
Douglas
S D
SD
Polin
R A
RA
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D009113:Muramidase / Q000096:biosynthesis*; D011506:Proteins / Q000378:metabolism
D005353:Fibronectins; D011506:Proteins; D004247:DNA; D009113:Muramidase; D000527:Alprostadil; D007930:Leucine; D007213:Indomethacin