Ablation of SP-A has a negative impact on the susceptibility of mice to Klebsiella pneumoniae infection after ozone exposure: sex differences.
Ablation of SP-A has a negative impact on the susceptibility of mice to Klebsiella pneumoniae infection after ozone exposure: sex differences.
复制标题
DOI：
10.1186/1465-9921-9-77
复制
发表时间：
2008-12-04
影响因子：
5.8
通讯作者：
Floros J
中科院分区：
文献类型：
--
作者：
Mikerov AN;Haque R;Gan X;Guo X;Phelps DS;Floros J
表面活性蛋白A（SP-A）增强肺泡巨噬细胞对包括肺炎克雷伯氏菌在内的细菌的吞噬作用。臭氧是一种主要的空气污染物，可引起肺表面活性物质的氧化，影响肺免疫功能。免疫功能也可能受到性别特异性机制的影响。我们假设SP-A的消融对臭氧暴露后小鼠对肺炎克雷伯菌感染的易感性有负面影响，并且臭氧的影响确实存在性别差异。以C57 BL/6 J为背景的SP-A（-/-）小鼠，分别暴露于臭氧或过滤空气（FA）中，然后用克雷伯氏菌（K.肺炎杆菌在14天期间监测存活率。此外，在接种用作假手术对照的PBS后1小时和接种K. pneumoniae细菌的PBS溶液中。结果表明：1）臭氧暴露后K.与暴露于过滤空气相比，肺炎克雷伯氏菌感染降低了SP-A（-/-）小鼠的存活率和肺泡巨噬细胞吞噬功能（p < 0.05），并且雌性比雄性受影响更大;在它们的存活率和巨噬细胞吞噬功能方面，FA SP-A（-/-）的肺炎小鼠的吞噬功能比野生型（WT）小鼠的吞噬功能高; FA SP-A（-/-）的吞噬功能与臭氧暴露的WT的吞噬功能相似。3)臭氧暴露似乎增加了WT小鼠中的PMNs、总蛋白和SP-A氧化的浸润; PMNs的浸润和总蛋白氧化似乎在雌性小鼠中对臭氧的响应更明显; 4）臭氧暴露增加WT雌性小鼠中的SP-A氧化显著多于雄性小鼠。SP-A（-/-）小鼠中SP-A的缺失（即SP-A的消融）或SP-A功能活性的降低（即WT小鼠中SP-A的氧化）增加了臭氧暴露后小鼠对实验性肺炎的易感性，并且在这两种情况下，雌性比雄性更受臭氧暴露的影响。
Surfactant protein A (SP-A) enhances phagocytosis of bacteria, including Klebsiella pneumoniae, by alveolar macrophages. Ozone, a major air pollutant, can cause oxidation of surfactant and may influence lung immune function. Immune function may also be affected by sex-specific mechanisms. We hypothesized that ablation of SP-A has a negative impact on the susceptibility of mice to Klebsiella pneumoniae infection after ozone exposure, and that sex differences in the effect of ozone do exist. Male and female SP-A (-/-) mice on the C57BL/6J background were exposed to ozone or to filtered air (FA) used as a control and then infected intratracheally with K. pneumoniae bacteria. Survival rate was monitored during a 14-day period. In addition, protein oxidation levels and in vivo phagocytosis were checked 1 h after inoculation of PBS used as a sham control and after inoculation of K. pneumoniae bacteria in PBS, respectively. We found: 1) ozone exposure followed by K. pneumoniae infection decreases survival and alveolar macrophage phagocytic function of SP-A (-/-) mice compared to filtered air exposure (p < 0.05), and females are more affected than males; 2) SP-A (-/-) mice (exposed either to ozone or FA) are more susceptible to infection with K. pneumoniae than wild type (WT) mice regarding their survival rate and macrophage phagocytic function; the phagocytic function of FA SP-A(-/-) is similar to that of ozone exposed WT. 3) ozone exposure appears to increase infiltration of PMNs, total protein, and SP-A oxidation in WT mice; infiltration of PMNs and total protein oxidation appears to be more pronounced in female mice in response to ozone; 4) ozone exposure increases SP-A oxidation in WT females significantly more than in males. Absence (i.e. ablation of SP-A in SP-A (-/-) mice) or reduction of functional activity of SP-A (i.e. oxidation of SP-A in WT mice) increases the susceptibility of mice to experimental pneumonia after ozone exposure, and in both cases females are more affected by ozone exposure than males.
登录
查看更多内容
DOI：
10.1152/ajplung.1998.275.4.l679
发表时间：
1998-10-01
影响因子：
4.9
作者：
Borron, P;McCormack, FX;Fraher, LJ
通讯作者：
Fraher, LJ
DOI：
10.1054/plef.2001.0309
发表时间：
2001-10-01
影响因子：
3
作者：
Blanco, O;Catalá, A
通讯作者：
Catalá, A
影响因子：
1.7
作者：
GILMOUR, MI;HMIELESKI, RR;JAKAB, GJ
通讯作者：
JAKAB, GJ
DOI：
10.1165/rcmb.2003-0246oc
发表时间：
2004-03-01
影响因子：
6.4
作者：
Hickman-Davis, JM;Gibbs-Erwin, J;Matalon, S
通讯作者：
Matalon, S
影响因子：
8.8
作者：
Abraham, E
通讯作者：
Abraham, E