Role of polymorphonuclear leukocyte-derived serine proteinases in defense against Actinobacillus actinomycetemcomitans
Role of polymorphonuclear leukocyte-derived serine proteinases in defense against Actinobacillus actinomycetemcomitans
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DOI：
10.1128/iai.02016-05
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发表时间：
2006-09-01
影响因子：
3.1
通讯作者：
Beertsen, Wouter
中科院分区：
文献类型：
--
作者：
de Haar, Susanne F.;Hiemstra, Pieter S.;Beertsen, Wouter
牙周炎是由伴放线放线杆菌等致病菌引起的牙齿支持组织的慢性破坏性感染。一种严重的牙周炎形式被发现在Papillon-Lefevre综合征（PLS）中，这是一种由组织蛋白酶C基因的功能丧失突变引起的遗传性疾病。最近，我们发现这些患者缺乏多形核白细胞（PMN）衍生的丝氨酸蛋白酶弹性蛋白酶，组织蛋白酶G和蛋白酶3的活性。在本研究中，我们确定了丝氨酸蛋白酶可能参与防御A。伴放线菌丝氨酸蛋白酶能够将PMN衍生的hCAP-18转化为LL-37，LL-37是一种具有抗A.伴放线菌我们发现PLS患者的PMNs释放较低水平的LL-37。此外，由于它们缺乏丝氨酸蛋白酶，PLS患者的PMN不能中和由该病原体产生的白细胞毒素，这导致细胞损伤增加。最后，检测了PLS患者PMNs对A.厌氧环境中的放线菌共生菌，如牙周袋中发现的，似乎减少。我们的报告证明了一种机制，表明PMN功能的遗传性缺陷和难以应对牙周炎相关病原体之间存在直接联系。
Periodontitis is a chronic destructive infection of the tooth-supportive tissues, which is caused by pathogenic bacteria such as Actinobacillus actinomycetemcomitans. A severe form of periodontitis is found in Papillon-Lefevre syndrome (PLS), an inheritable disease caused by loss-of-function mutations in the cathepsin C gene. Recently, we demonstrated that these patients lack the activity of the polymorphonuclear leukocyte (PMN)-derived serine proteinases elastase, cathepsin G, and proteinase 3. In the present study we identified possible pathways along which serine proteinases may be involved in the defense against A. actinomycetemcomitans. Serine proteinases are capable to convert the PMN-derived hCAP-18 into LL-37, an antimicrobial peptide with activity against A. actinomycetemcomitans. We found that the PMNs of PLS patients released lower levels of LL-37. Furthermore, because of their deficiency in serine proteases, the PMNs of PLS patients were incapable of neutralizing the leukotoxin produced by this pathogen, which resulted in increased cell damage. Finally, the capacity of PMNs from PLS patients to kill A. actinomycetemcomitans in an anaerobic environment, such as that found in the periodontal pocket, seemed to be reduced. Our report demonstrates a mechanism that suggests a direct link between an inheritable defect in PMN functioning and difficulty in coping with a periodontitis-associated pathogen.