The role of protegrins and other elastase-activated polypeptides in the bactericidal properties of porcine inflammatory fluids

被引:54
作者
Shi, JS
Ganz, T
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Will Rogers Inst Pulm Res Lab, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Sch Med, Dept Pathol, Will Rogers Inst Pulm Res Lab, Los Angeles, CA 90095 USA
关键词
D O I
10.1128/IAI.66.8.3611-3617.1998
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
mammalian host response to infection includes the production and secretion of antimicrobial peptides from phagocytes and epithelial cells. Protegrins, a group of broadly microbicidal peptides isolated originally from porcine neutrophil lysates, were found to he stored as inactive proforms in porcine neutrophil granules but could be activated extracellularly by neutrophil elastase, We assessed the biological role of protegrins and other elastase-activated polypeptides in the microbicidal activity of neutrophil secretions and inflammatory fluids. When stimulated with phorbol myristate acetate (PMA), neutrophils generated stable microbicidal activity against both Escherichia coli and Listeria monocytogenes under normal-salt conditions and in the presence of 0 to 10% serum. The generation of these antimicrobial substances was dependent on neutrophil elastase, since it was inhibited by 1 mM N-methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone when it was present during activation, but not when this inhibitor was added afterwards, However, elastase-dependent activation of proprotegrins to protegrins in PMA-stimulated neutrophils was not inhibited by the presence of 1 to 2% serum. Porcine neutrophils also released antibacterial activity during phagocytosis of latex beads, and this too was dependent in large part on elastase-activated polypeptides, including protegrins. Moreover, protegrins were found at bactericidal concentrations in cell-free abscess fluid from naturally infected pigs, Taken together, these studies show that protegrins and other elastase-activated polypeptides are important stable antibacterial factors in porcine neutrophil secretions, The potential host defense role of elastase as an activating enzyme for the precursors of microbicidal peptides must be taken into account when therapeutic inhibitors of neutrophil elastase are evaluated for clinical use as anti-inflammatory agents.
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页码:3611 / 3617
页数:7
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