title: Distinct and additive effects of elastase and endotoxin on expression of alpha 1 proteinase inhibitor in mononuclear phagocytes.
abstract: Expression of alpha 1 proteinase inhibitor (alpha 1-PI) in human mononuclear phagocytes may provide a local mechanism for inactivation of serine proteases at sites of tissue injury, thereby preventing incidental damage to surrounding tissue and allowing for orderly initiation of repair. We have previously shown that serine (neutrophilic or pancreatic) elastase and lipopolysaccharide (LPS) each mediate an increase in the expression of alpha 1-PI in human peripheral blood monocytes and bronchoalveolar macrophages. In this study we demonstrate that elastase and LPS have an additive positive regulatory effect on alpha 1-PI expression. Distinct pretranslational and translational mechanisms of action for elastase and LPS, respectively, account for the additive effect. The possibility that translational regulation of alpha 1-PI by LPS involves a mechanism analogous to that of the yeast gene GCN4 during amino acid starvation and that of the human ferritin gene in response to iron is discussed.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, Children's Hospital, St. Louis, Missouri 63110.
authors.forename: D H
authors.initials: DH
authors.lastname: Perlmutter
authors.forename: P I
authors.initials: PI
authors.lastname: Punsal
mesh_terms: D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D004347:Drug Interactions; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D000515:alpha 1-Antitrypsin
chemical_list: D001798:Blood Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase