Effect of hepatocyte-stimulating factor and glucocorticoids on plasma fibronectin levels.
We evaluated the effects of hepatocyte-stimulating factor (HSF) and a glucocorticoid (dexamethasone) on changes in the levels, in vivo and in vitro, of plasma fibronectin (Fn), a glycoprotein that is synthesized and secreted by hepatocytes. In turpentine-treated chickens, plasma levels of Fn, which peaked at 48 h (whereas fibrinogen levels were maximum at 72 h) rose 200-250% over basal levels, whereas albumin levels decreased by 20-40%. Corticosterone levels in serum samples taken between 5 and 48 h after injection revealed a 124% increase in hormone levels at 24 h in turpentine-treated chickens. We also showed that circulating HSF levels were maximal 8 to 12 h after injection and that HSF activity, as assessed by molecular-exclusion chromatography, was eluted in the 30-45 kDa range. Addition of either serum-derived HSF or dexamethasone (2 nM) to chick hepatocyte cultures resulted in a 130-150% increase in secreted Fn as well as in fibrinogen. When HSF and dexamethasone were added together, a 360-489% increase in the secreted levels of both proteins was found. Chicken mononuclear phagocytic cells treated with lipopolysaccharide secreted an HSF activity that was eluted in two peaks, a minor peak at approximately 70 kDa and a major peak in the 25-40 kDa range. Addition of mononuclear-cell-derived HSF resulted in a greater increase in Fn levels than did the addition of serum HSF. These findings indicate that Fn, like fibrinogen, is an acute-phase protein, the production of which, at least in chickens, is stimulated by HSF and glucocorticoids in an additive manner.
D000210:Acute-Phase Reaction / Q000097:blood; D000818:Animals; D002645:Chickens; D002850:Chromatography, Gel; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000097:blood*; D015850:Interleukin-6; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism
D005353:Fibronectins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011506:Proteins; D012709:Serum Albumin; D003907:Dexamethasone; D005340:Fibrinogen; D003345:Corticosterone