Meyer K C, Sharma A, Brown R, Weatherly M, Moya F R, Lewandoski J, Zimmerman J J
Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Wisconsin Medical School, Madison, WI, USA.
Chest. 2000 Jul;118(1):164-74. doi: 10.1378/chest.118.1.164.
To determine whether chronic lung inflammation in young adult patients with cystic fibrosis (CF) alters the composition and function of surfactant and surfactant components in bronchoalveolar secretions.
A prospective, descriptive study.
An adult CF center in a tertiary health-care center.
Thirteen normal volunteer (NV) subjects recruited via local advertising and 15 CF patients recruited from the CF center.
None.
We performed BAL and measured surfactant-associated protein A (SP-A) via enzyme-linked immunosorbent assay in BAL fluid (BALF), and quantitated total phospholipid, phospholipid subclass, and fatty acid subclass content of extracted BALF. We also determined the protein and phospholipid content, SP-A content, and functional characteristics of surfactant isolated from BALF via high-speed centrifugation. The phospholipid-to-protein ratio (milligram/milligram) of surfactant isolated by centrifugation (mean +/- SEM) was 1.01 +/- 0.07 for NV subjects and 2.62 +/- 0.42 for CF patients (p = 0.0001). Minimal surface tension was < 1 dyne.s.cm(-5) in all samples from NV subjects, but 21.9 +/- 0.73 dyne.s.cm(-5) for surfactant from CF patients. Immunoblotting of isolated surfactant revealed a marked decrease in SP-A for CF patients, compared to NV subjects. However, mean concentrations of SP-A in BALF that had not been subjected to high-speed centrifugation to isolate surfactant were not significantly different for CF patients (4.7 +/- 0.8 microgram/mL) vs NV subjects (4.6 +/- 0.2 microgram/mL). Additionally, phospholipid-to-protein ratios (0.32 +/- 0.04 for NV subjects vs 0.10 +/- 0.02 for CF patients; p < 0.0001) in extracted uncentrifuged BALF, and SP-A-to-protein ratios (microgram/milligram) in BALF were significantly depressed (74 +/- 8 for NV subjects vs 16 +/- 3 for CF patients; p < 0.0001). The phospholipid and fatty acid subclass profiles of extracted CF BALF vs NV BALF revealed a decreased mean phosphatidylcholine-to-sphingomyelin ratio (20.7 +/- 10.0 vs 55.2 +/- 8.7; p = 0.002), increased oleic acid content (12.1 +/- 2.3 nmol/mL vs 3.2 +/- 0.9 nmol/mL; p < 0.01), and increased arachidonic acid content (2.2 +/- 0.5 nmol/mL vs 0.6 +/- 0.3 nmol/mL; p < 0.05) for CF patients.
Altered phospholipid-to-protein ratios and phospholipid subclasses, altered surfactant-derived fatty acid profiles, high minimal surface tension, and decreased association of SP-A with lipid components of isolated surfactant indicate that surfactant components are considerably altered and dysfunctional in lower respiratory tract secretions of CF patients. Surfactant composition and function are altered in CF, and the pattern of phospholipid and surfactant-derived fatty acid subclass alterations in CF are characteristic of ongoing lung injury and may depress surfactant function.
确定患有囊性纤维化（CF）的年轻成年患者的慢性肺部炎症是否会改变支气管肺泡分泌物中表面活性剂及其成分的组成和功能。
一项前瞻性描述性研究。
一家三级医疗保健中心的成人CF中心。
通过当地广告招募的13名正常志愿者（NV）受试者和从CF中心招募的15名CF患者。
无。
我们进行了支气管肺泡灌洗（BAL），并通过酶联免疫吸附测定法在支气管肺泡灌洗液（BALF）中测量了表面活性剂相关蛋白A（SP-A），并对提取的BALF中的总磷脂、磷脂亚类和脂肪酸亚类含量进行了定量。我们还通过高速离心法测定了从BALF中分离出的表面活性剂的蛋白质和磷脂含量、SP-A含量以及功能特性。通过离心分离的表面活性剂的磷脂与蛋白质比率（毫克/毫克）（均值±标准误），NV受试者为1.01±0.07，CF患者为2.62±0.42（p = 0.0001）。NV受试者所有样本的最小表面张力<1达因·秒·厘米⁻⁵，而CF患者表面活性剂的最小表面张力为21.9±0.73达因·秒·厘米⁻⁵。对分离出的表面活性剂进行免疫印迹分析显示，与NV受试者相比，CF患者的SP-A显著降低。然而，未经过高速离心分离表面活性剂的BALF中，CF患者的SP-A平均浓度（4.7±0.8微克/毫升）与NV受试者（4.6±0.2微克/毫升）相比无显著差异。此外，提取的未离心BALF中的磷脂与蛋白质比率（NV受试者为0.32±0.04，CF患者为0.10±0.02；p<0.0001）以及BALF中的SP-A与蛋白质比率（微克/毫克）显著降低（NV受试者为74±8，CF患者为16±3；p<0.0001）。提取的CF BALF与NV BALF的磷脂和脂肪酸亚类谱显示，CF患者的平均磷脂酰胆碱与鞘磷脂比率降低（20.7±10.0对55.2±8.7；p = 0.002），油酸含量增加（12.1±2.3纳摩尔/毫升对3.2±0.9纳摩尔/毫升；p<0.01），花生四烯酸含量增加（2.2±0.5纳摩尔/毫升对0.6±0.3纳摩尔/毫升；p<0.05）。
磷脂与蛋白质比率和磷脂亚类的改变、表面活性剂衍生脂肪酸谱的改变、高最小表面张力以及SP-A与分离出的表面活性剂脂质成分的结合减少表明，CF患者下呼吸道分泌物中的表面活性剂成分发生了显著改变且功能失调。CF患者的表面活性剂组成和功能发生改变，CF中磷脂和表面活性剂衍生脂肪酸亚类改变的模式是持续肺损伤的特征，可能会降低表面活性剂的功能。
