Protective effect of recombinant neutrophil elastase inhibitor (R-020) on sepsis-induced organ injury in rat.
Severe inflammatory responses after major surgeries, trauma, and infection develop multiple organ dysfunction. In the mechanisms of the pathogenesis of these responses, activated neutrophils are thought to be important in terms of their ability to produce various kinds of proteinases, which can degrade various proteins constructing human tissues. Among their proteinases, neutrophil elastase is the strongest serine proteinase secreted from activated neutrophils. Thus, we examined in this study the inhibitory effect and therapeutic efficacy of newly produced recombinant human Kunitz-type proteinase inhibitor (R-020), which coded the second domain of human urinary trypsin inhibitor. R-020 was effective in significantly improving the survival rate after induction of the rat lethal peritonitis model (cecal ligation and puncture-induced septic shock model). We suggest that various serine proteinases are implicated in the pathogenesis of neutrophil-related multiple organ failure and that recombinant human Kunitz-type proteinase inhibitor might be effective in the treatment of these kinds of organ dysfunction.
Murata
A
A
Department of Surgery II, Osaka University Medical School, Japan.
Toda
H
H
Uda
K
K
Hayashida
H
H
Kato
T
T
Nakagawa
H
H
Yokoyama
S
S
Morishita
H
H
Yamakawa
T
T
Hirose
J
J
D000595:Amino Acid Sequence; D000818:Animals; D007611:Aprotinin / Q000235:genetics / Q000494:pharmacology*; D002432:Cecum; D006023:Glycoproteins / Q000235:genetics; D007239:Infections / Q000401:mortality / Q000473:pathology*; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D010538:Peritonitis / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D016019:Survival Analysis; D014361:Trypsin Inhibitors / Q000235:genetics
D006023:Glycoproteins; D011994:Recombinant Proteins; D014361:Trypsin Inhibitors; C090706:recombinant neutrophil elastase inhibitor R-020; D007611:Aprotinin; C028665:urinastatin