Inhibition of human, ovine, and baboon neutrophil elastase with Eglin c and secretory leukocyte proteinase inhibitor.
The association rate constants (kon) of human, ovine, and baboon neutrophil elastase with two recombinant serine proteinase inhibitors (Eglin c, secretory leukocyte proteinase inhibitor) were compared. The association rate constant of sheep leukocyte elastase (SLE) with Eglin c is about 100 times lower (kon = 2.2 x 10(5) M-1s-1) than that of human elastase (kon = 2.4 x 10(7) M-1s-1). Baboon elastase, however, is as effectively blocked with Eglin c (kon = 2.5 x 10(7) M-1s-1) as human elastase. Secretory leukocyte proteinase inhibitor (SLPI) blocks the elastase of all three species with high efficiency; baboon elastase shows the highest association rate constant (kon = 5.6 x 10(7) M-1s-1) followed by human elastase (kon = 4.1 x 10(7) M-1s-1) and finally sheep elastase (kon = 1.2 x 10(7) M-1s-1). These findings demonstrate marked differences in the inhibition kinetic properties of ovine and human elastase. Concerning a future clinical application of proteinase inhibitors, the baboon seems a more suitable model than sheep to evaluate the effects of Eglin c and SLPI, since both inhibitors block baboon and human elastase with comparable efficiency.
Department of Surgery, University of California San Diego.
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Junger
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Hallström
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Redl
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Schlag
D000818:Animals; D006801:Humans; D019272:Leukocyte Elastase; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010215:Papio; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015843:Serpins; D012756:Sheep
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C028656:eglin proteinase inhibitors; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase