title: Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress.
abstract: Secretory leukoprotease inhibitor (SLPI) and alpha 1-protease inhibitor (alpha 1-PI) are powerful antiproteases currently under investigation for their potential to protect the lung from neutrophil elastase (NE). The aim of this study was to determine whether the recombinant form of SLPI (rSLPI) and alpha 1-PI show different grades of loss of inhibitory activity when exposed to reactive oxygen metabolites. We incubated rSLPI and alpha 1-PI with N-chlorosuccinimide (NCS), chloramines, activated polymorphonuclear leucocytes (PMNs) and activated alveolar macrophages (AMs). Under all conditions evaluated, both antiproteases were partially inactivated. The resulting anti-NE activity of rSLPI was not significantly different from that of alpha 1-PI after exposure to NCS (p > 0.5), chloramines (p > 0.6), activated PMNs (p > 0.07) and activated AMs (p > 0.9). In conclusion, recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor lose antineutrophil elastase activity to a similar extent when exposed to conditions that may be present in inflammatory lung disorders.
authors.affiliation: Pneumologische Abteilung, Medizinische Klinik I, Klinikum Grosshadern, University of Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Vogelmeier
authors.forename: T
authors.initials: T
authors.lastname: Biedermann
authors.forename: K
authors.initials: K
authors.lastname: Maier
authors.forename: G
authors.initials: G
authors.lastname: Mazur
authors.forename: J
authors.initials: J
authors.lastname: Behr
authors.forename: F
authors.initials: F
authors.lastname: Krombach
authors.forename: R
authors.initials: R
authors.lastname: Buhl
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002700:Chloramines / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008252:Macaca fascicularis; D016676:Macrophages, Alveolar / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D002700:Chloramines; D016877:Oxidants; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D013388:Succinimides; D000515:alpha 1-Antitrypsin; C015752:N-chlorosuccinimide; D019272:Leukocyte Elastase