Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism
Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism
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DOI：
10.1165/rcmb.2003-0091oc
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发表时间：
2004-03-01
影响因子：
6.4
通讯作者：
Gow, AJ
中科院分区：
文献类型：
--
作者：
Atochina, EN;Beers, MF;Gow, AJ
表面活性蛋白D（SurfactantProtein，SP）是一种43 kD的多功能胶原样凝集素，由气道上皮细胞合成和分泌。SP-D敲除（SP-D [-/-]）小鼠表现出气道巨噬细胞数量和大小增加、细支气管周围炎症、金属蛋白酶活性增加和肺气肿发展。一氧化氮（NO）参与多种信号传导过程，并且由于在炎症中观察到NO代谢的改变，我们假设其代谢的改变是在SP-D缺乏中观察到的促炎状态的基础。对SP-D（-/-）小鼠支气管肺泡灌洗（BAL）的检查显示蛋白质和磷脂含量以及总细胞计数显著增加。NO的产生和诱导型NO合酶的表达增加在BAL中，但是，有一个下降的S-亚硝基硫醇（SNO）的含量在BAL和损失的SNO免疫反应性的组织内。这种SNO的下降伴随着硝基酪氨酸染色的增加。我们的结论是，炎症发生在SP-D缺乏导致NO产生的增加和NO的化学和目标的转变。我们推测，由于SP-D缺乏的促炎反应的结果，在一定程度上，从先天免疫系统内的NO介导的信号中断。
Surfactant protein (SP)-D, a 43-kD multifunctional collagen-like lectin, is synthesized and secreted by the airway epithelium. SP-D knockout (SP-D [-/-]) mice exhibit an increase in the number and size of airway macrophages, peribronchiolar inflammation, increases in metalloproteinase activity, and development of emphysema. Nitric oxide (NO) is involved in a variety of signaling processes, and because altered NO metabolism has been observed in inflammation, we hypothesized that alterations in its metabolism would underlie the proinflammatory state observed in SP-D deficiency. Examination of the bronchial alveolar lavage (BAL) from SP-D (-/-) mice reveals a significant increase in protein and phospholipid content and total cell count. NO production and inducible NO synthase expression were increased in the BAL; however, there was a decline in S-nitrosothiol (SNO) content in the BAL and a loss of SNO immunoreactivity within the tissue. This decline in SNO was accompanied by an increase in nitrotyrosine staining. We conclude that inflammation that occurs in SP-D deficiency results in an increase in NO production and a shift in the chemistry and targets of NO. We speculate that the proinflammatory response due to SP-D deficiency results, in part, from a disruption of NO-mediated signaling within the innate immune system.