The lactoperoxidase system functions in bacterial clearance of airways
The lactoperoxidase system functions in bacterial clearance of airways
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DOI：
10.1165/ajrcmb.22.6.3980
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发表时间：
2000-06-01
影响因子：
6.4
通讯作者：
Conner, GE
中科院分区：
文献类型：
--
作者：
Gerson, C;Sabater, J;Conner, GE
气道粘液是一种分泌产物的复杂混合物，提供了多方面的防御肺部感染。粘液含有抗微生物肽（例如，防御素）和酶（例如，溶菌酶），尽管这些对气道无菌性的贡献尚未在体内测试。我们以前已经表明，酶活性，含血红素过氧化物酶包括1%的可溶性蛋白质在绵羊气道分泌物中，它已被假设，这种气道过氧化物酶可以作为一种生物杀灭系统的功能。在这项研究中，我们表明，绵羊气道过氧化物酶是相同的牛奶乳过氧化物酶（LPO）和绵羊气道分泌物中含有硫氰酸盐（SCN）的浓度必要和足够的功能过氧化物酶系统，可以防止感染。我们还表明，呼吸道LPO，像牛奶LPO，在体外产生杀生物化合物次硫氰酸盐（OSCN）。最后，我们表明，在体内抑制绵羊气道LPO导致从气道细菌清除显着减少。这些数据表明，LPO系统是气道防御的主要贡献者。这一发现可能对囊性纤维化等呼吸系统疾病中的慢性气道定植具有重要意义。
Airway mucus is a complex mixture of secretory products that provides a multifaceted defense against pulmonary infection. Mucus contains antimicrobial peptides (e.g., defensins) and enzymes (e.g., lysozyme) although the contribution of these to airway sterility has not been tested in vivo. We have previously shown that an enzymatically active, heme-containing peroxidase comprises 1% of the soluble protein in sheep airway secretions, and it has been hypothesized that this airway peroxidase may function as a biocidal system. In this study, we show that sheep airway peroxidase is identical to milk lactoperoxidase (LPO) and that sheep airway secretions contain thiocyanate (SCN) at concentrations necessary and sufficient for a functional peroxidase system that can protect against infection. We also show that airway LPO, like milk LPO, produces the biocidal compound hypothiocyanite (OSCN) in vitro. Finally, we show that in vivo inhibition of airway LPO in sheep leads to a significant decrease in bacterial clearance from the airways. The data suggest that the LPO system is a major contributor to airway defenses. This discovery may have significant implications for chronic airway colonization seen in respiratory diseases such as cystic fibrosis.