Effect of surfactant on pulmonary expression of type IIA PLA2 in an animal model of acute lung injury
Effect of surfactant on pulmonary expression of type IIA PLA2 in an animal model of acute lung injury
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DOI：
10.1152/ajplung.00181.2001
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发表时间：
2002-04-01
影响因子：
4.9
通讯作者：
Touqui, L
中科院分区：
文献类型：
--
作者：
Wu, YZ;Singer, M;Touqui, L
我们以前发现，天然表面活性剂固尔苏抑制肺泡巨噬细胞（AM）分泌型IIA型磷脂酶A（2）（sPLA（2）-IIA）的体外合成。这些细胞是脂多糖（LPS）诱导的急性肺损伤（ALI）豚鼠模型中sPLA（2）-IIA的主要来源。在此，我们研究了固尔苏对该ALI模型中sPLA（2）-IIA的肺合成的影响。我们的研究结果表明，肺内注射LPS（330 μ g/kg）可诱导sPLA（2）-IIA的肺表达增加，而在LPS滴注后30 min或8 h给予Curosurf（16 mg/豚鼠）可抑制sPLA（2）-IIA的表达。当从脂多糖处理的动物中分离AM并在条件培养基中培养时，它们比盐水处理的动物中的AM表达更高水平的sPLA（2）-IIA。当豚鼠在LPS滴注后30分钟接受固尔苏时，这种离体sPLA（2）-IIA表达显著降低。最后，我们检查了固尔苏对LPS给药后8或24小时测量的肺部炎症的影响。LPS后30 min或8 h滴注固尔苏可逆转肿瘤坏死因子-α表达、多形核细胞外渗和支气管肺泡灌洗液中蛋白浓度的增加。固尔苏还降低LPS诱导的支气管反应性。我们得出结论，固尔苏抑制sPLA（2）-IIA的肺表达，并在ALI动物模型中表现出姑息性抗炎作用。
We previously showed that the seminatural surfactant Curosurf inhibits the in vitro synthesis of secretory type IIA phospholipase A(2) (sPLA(2)-IIA) in alveolar macrophages (AM). These cells are the main source of sPLA(2)-IIA in a guinea pig model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Here, we investigate the effect of Curosurf on the pulmonary synthesis of sPLA(2)-IIA in this ALI model. Our results showed that intratracheal administration of LPS (330 mug/kg) induced an increase in pulmonary expression of sPLA(2)-IIA, which was inhibited when animals received Curosurf (16 mg/guinea pig) 30 min or 8 h after LPS instillation. When AM were isolated from LPS-treated animals and cultured in conditioned medium, they expressed higher levels of sPLA(2)-IIA than AM from saline-treated animals. This ex vivo sPLA(2)-IIA expression was significantly reduced when guinea pigs received Curosurf 30 min after LPS instillation. Finally, we examined the effect of Curosurf on pulmonary inflammation measured 8 or 24 h after LPS administration. Curosurf instillation 30 min or 8 h after LPS reversed the increase in tumor necrosis factor-alpha expression, polymorphonuclear cell extravasation, and protein concentration in bronchoalveolar lavage fluids. Curosurf also decreased the bronchial reactivity induced by LPS. We conclude that Curosurf inhibits the pulmonary expression of sPLA(2)-IIA and exhibits palliative anti-inflammatory effects in an animal model of ALI.