Induction of hepatocyte synthesis of fibronectin by a non-interleukin-1 monokine.
Plasma fibronectin concentrations initially decrease and then markedly increase following injury and during inflammation. Although hepatocytes are known to be the major source of plasma fibronectin, the stimulus controlling its production is not known. The present study investigated the role of interleukin-1 (Il-1) and LPS-induced monocyte supernatants in stimulating hepatocyte fibronectin synthesis in vitro. Hepatocytes exposed to monocyte supernatants significantly increased their production of fibronectin and fibrinogen. Albumin production was suppressed. Both LPS-induced and noninduced monocyte supernatants increased hepatocyte fibronectin and fibrinogen synthesis, and decreased albumin synthesis. However, only LPS-induced monocyte supernatants contained Il-1 activity. Pure Il-1 had no effect on hepatocyte fibronectin synthesis. Molecular sizing of the monocyte supernatants containing the Fibronectin Stimulating Factor (FSF) yielded active fractions in the 30-40 kD range. These fractions did not contain Il-1 activity. We conclude that a non-Il-1 monokine, Fibronectin Stimulating Factor (FSF), stimulates hepatocyte production of fibronectin. FSF is presumably the monokine responsible for stimulating hepatocyte fibronectin production in vivo following injury and during inflammation. Based on these results, and the time-course of fibronectin levels seen following injury and during inflammation, it seems reasonable to consider fibronectin as one of the acute-phase proteins.
Lanser
M E
ME
Department of Surgery, Beth Israel Hospital, Boston, MA 02215.
Brown
G E
GE
D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D001688:Biological Products / Q000502:physiology*; D002478:Cells, Cultured; D003470:Culture Media; D005340:Fibrinogen / Q000096:biosynthesis; D005353:Fibronectins / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000502:physiology*; D015846:Monokines; D051381:Rats; D011919:Rats, Inbred Strains
D000418:Albumins; D001688:Biological Products; D003470:Culture Media; D005353:Fibronectins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D015846:Monokines; D005340:Fibrinogen