Lung function in premature rabbits treated with recombinant human surfactant protein-C
Lung function in premature rabbits treated with recombinant human surfactant protein-C
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DOI：
10.1164/ajrccm.154.2.8756826
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发表时间：
1996-08-01
影响因子：
24.7
通讯作者：
Benson, B
中科院分区：
文献类型：
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作者：
Hawgood, S;Ogawa, A;Benson, B
我们报道了重组人表面活性剂载脂蛋白c （rSP-C[Cys](2)）和多种磷脂在早产兔呼吸窘迫综合征（RDS）模型中的活性。在该模型中，rSP-C(Cys)(2)和某些磷脂的混合物具有与兔表面活性剂相似的活性（肺顺应性和肺压力-容积行为）。rSP-C(Cys)(2)的活性在蛋白质含量为1 mol%时最高，且随磷脂组成的变化而显著变化。化学合成的SP-C具有与rSP-C（Cys）相似的活性(2)。6个氨基末端残基的缺失不影响功能。通过位点特异性诱变将半胱氨酸和半胱氨酸替换为相邻丝氨酸（rSP-C[Ser](2)），可减少rSP-C的聚集，但不影响其活性。rSP-C（rSP-C[C16](2)）的半胱氨酸和半胱氨酸棕榈酰化并没有增强rSP-C（Cys）的活性(2)。我们得出结论，细菌表达是功能性SP-C的一个实际来源，非酰化形式的SP-C可能是治疗RDS和其他形式的急性肺损伤中有用的磷脂佐剂。
We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys](2)) and various phospholipids in a preterm rabbit model of respiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)(2) and certain phospholipids had similar activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)(2) was maximal at 1 mol% protein and varied significantly with the phospholipid composition. Chemically synthesized SP-C had similar activity to rSP-C(Cys)(2). Deletion of six amino-terminal residues did not affect function. Substitution of cysteines and cysteines with adjacent serines (rSP-C[Ser](2)) by site-specific mutagenesis minimized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteines and cysteines in rSP-C (rSP-C[C16](2)) did not enhance the activity of rSP-C(Cys)(2). We conclude that bacterial expression is a practical source of functional SP-C, and that nonacylated forms of SP-C may be useful adjuvants to phospholipids in the treatment of RDS and possibly other forms of acute lung injury.