Increased phospholipase A2 and lyso-phosphatidylcholine levels are associated with surfactant dysfunction in lung contusion injury in mice.
Increased phospholipase A2 and lyso-phosphatidylcholine levels are associated with surfactant dysfunction in lung contusion injury in mice.
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DOI：
10.1016/j.surg.2012.05.043
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发表时间：
2013-01
期刊：
影响因子：
3.8
通讯作者：
Raghavendran, Krishnan
中科院分区：
文献类型：
--
作者：
Machado-Aranda, David;Wang, Zhengdong;Yu, Bi;Suresh, M. V.;Notter, Robert H.;Raghavendran, Krishnan
表面活性剂功能障碍是各种形式的急性炎症性肺损伤中重要的病理紊乱。此前，我们报道了钝性创伤引起的大鼠双侧肺挫伤（LC）损伤中肺表面活性物质的成分和活性存在显着变化。这里将其扩展到单侧 LC 小鼠模型，重点关注与通透性损伤相关的成分和功能性表面活性剂变化以及分泌性磷脂酶 A2 活性的增加。根据 Affymetrix 分析，单侧 LC 损伤小鼠中表面活性剂相关基因表达没有显着改变。与未受伤的对照组相比，LC小鼠在受到攻击后5、24、48和72小时时出现明显的通透性损伤，支气管肺泡灌洗液(BAL)中的白蛋白和总蛋白增加。在损伤后的所有时间内，大表面活性剂聚集体的百分比含量均显着减少，并且在此期间肺动脉压力-容积（P-V）力学和顺应性异常。在 24 小时时对表面活性剂功能障碍进行机制细节评估，此时渗透性损伤和 P-V 变化最为突出。此时，BAL 中分泌型磷脂酶 A2 (PLA2) 的活性水平升高，色谱分析表明，大的表面活性剂聚集体导致磷脂酰胆碱 (PC) 水平降低，溶血 PC 水平升高。这些变化伴随着脉动气泡表面活性测定法对大聚集体表面活性的严重损害。长时间气泡脉动（20 分钟）后，24 小时 LC 小鼠的大聚集体的最小表面张力仅为 12.6±1.1 mN/m，而未受伤对照的表面张力为 0.7±0.03 mN/m。这些结果证明了小鼠 LC 损伤中肺表面活性剂的组成和活性受到显着损害，并表明活性合成的抗磷脂酶外源性表面活性剂可能在治疗这种临床重要病症中的表面活性剂功能障碍方面具有未来的用途。
Surfactant dysfunction is an important pathological disturbance in various forms of acute inflammatory lung injury. Previously we reported the presence of significant alterations in the composition and activity of pulmonary surfactant in blunt trauma-induced bilateral lung contusion (LC) injury in rats. This is extended here to a mouse model of unilateral LC, with a focus on compositional and functional surfactant changes associated with permeability injury and increases in activity of secretory phospholipase A2. Surfactant-associated gene expression was not significantly altered in mice with unilateral LC injury based on Affymetrix analysis. LC mice had significant permeability injury with increased albumin and total protein in bronchoalveolar lavage (BAL) at 5, 24, 48 and 72 h post-insult compared to uninjured controls. The percent content of large surfactant aggregates was significantly depleted at all post-injury times, and pulmonary pressure-volume (P-V) mechanics and compliance were abnormal over this period. Surfactant dysfunction was evaluated in mechanistic detail at 24 h, when permeability injury and P-V changes were most prominent. At this time, activity levels of secretory phospholipase A2 (PLA2) were increased in BAL, and chromatographic analysis showed that large surfactant aggregates had decreased levels of phosphatidylcholine (PC) and increased levels of lyso-PC. These changes were accompanied by severe detriments in large aggregate surface activity by pulsating bubble surfactometry. Large aggregates from LC mice at 24 h had minimum surface tensions of only 12.6±1.1 mN/m after prolonged bubble pulsation (20 min) compared to 0.7±0.03 mN/m for uninjured controls. These results document significant detriments in the composition and activity of pulmonary surfactant in LC injury in mice, and suggest that active synthetic phospholipase-resistant exogenous surfactants may have future utility in treating surfactant dysfunction in this clinically-important condition.
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DOI：
10.1152/ajplung.00229.2004
发表时间：
2005-04-01
影响因子：
4.9
作者：
Davidson, BA;Knight, PR;Notter, RH
通讯作者：
Notter, RH
影响因子：
15.9
作者：
HALLMAN, M;SPRAGG, R;GLUCK, L
通讯作者：
GLUCK, L
影响因子：
3.3
作者：
LEWIS, JF;IKEGAMI, M;JOBE, AH
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影响因子：
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作者：
HOLM, BA;NOTTER, RH;FINKELSTEIN, JN
通讯作者：
FINKELSTEIN, JN
DOI：
10.1164/ajrccm.149.5.8173747
发表时间：
1994-05-01
影响因子：
24.7
作者：
HALL, SB;HYDE, RW;NOTTER, RH
通讯作者：
NOTTER, RH