A novel lung injury animal model using KL-6-measurable human MUC1-expressing mice
A novel lung injury animal model using KL-6-measurable human MUC1-expressing mice
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DOI：
10.1016/j.bbrc.2013.01.123
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发表时间：
2013-03-15
影响因子：
3.1
通讯作者：
Yokoyama, Akihito
中科院分区：
文献类型：
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作者：
Sakai, Mizu;Kubota, Tetsuya;Yokoyama, Akihito
KL-6是人类II型肺细胞和细支气管上皮细胞上表达的MUC 1粘蛋白的表位，是间质性肺炎的敏感血清标志物。然而，KL-6的体内模型尚未建立，因为KL-6表位在除人和猿以外的动物中不表达。为了研究KL-6在人MUC 1表达（hMUC 1-exp）小鼠中是否可检测到以及KL-6水平是否反映肺损伤的程度，我们检测了脂多糖（LPS）或博莱霉素（BLM）诱导的肺损伤模型中KL-6和表面活性蛋白-D（SP-D）的血清和支气管肺泡灌洗液（BALF）水平。KL-6在幼稚hMUC 1-exp小鼠的II型肺细胞和细支气管上皮细胞上表达。这些小鼠中的血清KL-6水平与人中的血清KL-6水平相当，BALE中的KL-6水平显著高于血清中的KL-6水平。在LPS模型中，血清和BALF中KL-6水平略有升高，但SP-D水平显著升高。在BLM模型的炎症阶段，血清中KL-6水平显著升高，而BALF中KL-6水平降低。血清KL-6水平与BALE白蛋白水平呈正相关，BALE白蛋白水平是肺泡毛细血管通透性增加的代表性标志物。血清和BALE中的SP-D水平与LPS模型中的相应水平相比显著增加。血清KL-6水平的增加似乎与BLM诱导的肺损伤后肺泡-毛细血管屏障的破坏有关。该hMUC 1-exp小鼠可用于在肺损伤期间体内评估KL-6。(C)2013 Elsevier Inc. All rights reserved.
KL-6, an epitope of MUC1 mucin expressed on type II pneumocytes and bronchiolar epithelia in humans, is a sensitive serum marker for interstitial pneumonia. However, an in vivo model for KL-6 has not been established because no KL-6 epitope is expressed in animals other than humans and apes. To investigate whether KL-6 is detectable in human MUC1-expressing (hMUC1-exp) mice and whether KL-6 level reflects the degree of lung injury, we examined serum and bronchoalveolar lavage fluid (BALF) levels of KL-6 and surfactant protein-D (SP-D) in either lipopolysaccharide (LPS)- or bleomycin (BLM)-induced lung injury models. KL-6 was expressed on type II pneumocytes and bronchiolar epithelial cells in naive hMUC1-exp mice. Serum KL-6 levels in these mice were comparable to those in humans, and KL-6 levels in BALE were significantly higher than those in sera. In the LPS model, KL-6 levels in sera and BALF were slightly increased, although SP-D levels were markedly increased. During the inflammatory phase in the BLM model, KL-6 levels in sera were greatly increased, but those in BALF were decreased. Serum KL-6 levels were positively correlated with BALE albumin levels, a representative marker for increased the alveolar-capillary permeability. SP-D levels in sera and BALE were significantly increased compared to the corresponding levels in the LPS model. The increase in serum KL-6 levels appeared to be associated with the disruption of alveolar-capillary barrier after BLM-induced lung injury. This hMUC1-exp mouse can be used for assessment of KL-6 in vivo during lung injury. (C) 2013 Elsevier Inc. All rights reserved.