Keratinocyte growth factor protects against Pseudomonas aeruginosa-induced lung injury

Keratinocyte growth factor protects against Pseudomonas aeruginosa-induced lung injury
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DOI:
10.1152/ajplung.2000.279.6.l1199
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发表时间:
2000-12-01
影响因子:
4.9
通讯作者:
Pittet, JF
Pittet, JF
中科院分区:
医学2区
文献类型:
--
作者:
Viget, NB;Guery, BPH;Pittet, JF

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我们以前曾报道过角质细胞生长因子(KGF)通过上调肺泡液体转运来减轻α-萘基硫脲诱导的肺损伤。本研究的目的是确定KGF预处理在铜绿假单胞菌肺炎中的作用。在肺内滴入铜绿假单胞菌后4或24 h,将含1 μ Ci I-125标记人白蛋白的5%牛白蛋白溶液滴入空气间隙,并将1 h内远端空气间隙中未标记和标记蛋白的浓度用作净肺泡液清除率的指标。通过血管内注射1 mCi I-131-白蛋白评价肺泡毛细血管屏障通透性。在早期肺炎,KGF增加肺液体清除率(LLC)相比,在nonpretreated动物。在晚期肺炎,LLC显着减少,在没有KGF,但增加高于对照值与KGF。KGF预处理增加了支气管肺泡灌洗液中多形核细胞的数量,减少了细菌的肺移位。总之,KGF在铜绿假单胞菌肺炎急性期恢复正常肺泡上皮细胞液体转运,在早期和晚期肺炎中恢复LLC。宿主反应也得到改善,如肺泡细胞反应的增加和细菌肺移位的减少所示。
We have previously reported that keratinocyte growth factor (KGF) attenuates alpha -naphthylthiourea-induced lung injury by upregulating alveolar fluid transport. The objective of this study was to determine the effect of KGF pretreatment in Pseudomonas aeruginosa pneumonia. A 5% bovine albumin solution with 1 mu Ci of I-125-labeled human albumin was instilled into the air spaces 4 or 24 h after intratracheal instillation of P. aeruginosa, and the concentration of unlabeled and labeled proteins in the distal air spaces over 1 h was used as an index of net alveolar fluid clearance. Alveolocapillary barrier permeability was evaluated with an intravascular injection of 1 mCi of I-131-albumin. In early pneumonia, KGF increased lung liquid clearance (LLC) compared with that in nonpretreated animals. In late pneumonia, LLC was significantly reduced in the absence of KGF but increased above the control value with KGF. KGF pretreatment increased the number of polymorphonuclear cells recovered in the bronchoalveolar lavage fluid and decreased bacterial pulmonary translocation. In conclusion, KGF restores normal alveolar epithelial fluid transport during the acute phase of P. aeruginosa pneumonia and LLC in early and late pneumonia. Host response is also improved as shown by the increase in the alveolar cellular response and the decrease in pulmonary translocation of bacteria.