title: Human neutrophil defensin and serpins form complexes and inactivate each other.
abstract: Defensins, antimicrobial and cytotoxic peptides of neutrophils, bind to and are inactivated by blood proteins. We identified defensin interactions with alpha 1-proteinase inhibitor (alpha 1-PI), alpha 1-antichymotrypsin (alpha 1-ACT), alpha 2-antiplasmin (alpha 2-AP), and antithrombin III (AT III) and examined defensin binding to alpha 1-PI and alpha 1-ACT in more detail. Defensin interactions with either alpha 1-PI or alpha 1-ACT were not affected by iodoacetamide or high salt concentration. Preincubation of alpha 1-ACT or alpha 1-PI with increasing concentrations of defensin resulted in a progressive decrease of antiprotease activity of both inhibitors against cathepsin G and antiprotease activity of alpha 1-PI against human neutrophil elastase. At higher concentrations, defensin also ablated the inhibitory effect of normal human serum on cathepsin G and human neutrophil elastase. Both alpha 1-PI and alpha 1-ACT inhibited defensin cytotoxicity toward the human lung carcinoma cell line A549, whereas the elastase inhibitor antileukoprotease did not. Complex interactions between serpins and defensin may have a role in regulating inflammatory processes.
authors.affiliation: Will Rogers Pulmonary Research Laboratory, University of California at Los Angeles 90024-1736.
authors.forename: A V
authors.initials: AV
authors.lastname: Panyutich
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: S
authors.initials: S
authors.lastname: van Wetering
authors.forename: T
authors.initials: T
authors.lastname: Ganz
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D023082:Defensins; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D009504:Neutrophils / Q000201:enzymology*; D011485:Protein Binding; D015843:Serpins / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D023082:Defensins; D046911:Macromolecular Substances; D015843:Serpins