IDENTIFICATION AND PARTIAL CHARACTERIZATION OF ANGIOGENESIS BIOACTIVITY IN THE LOWER RESPIRATORY-TRACT AFTER ACUTE LUNG INJURY
IDENTIFICATION AND PARTIAL CHARACTERIZATION OF ANGIOGENESIS BIOACTIVITY IN THE LOWER RESPIRATORY-TRACT AFTER ACUTE LUNG INJURY
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DOI：
10.1172/jci115445
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发表时间：
1991-10-01
影响因子：
15.9
通讯作者：
BITTERMAN, P
中科院分区：
文献类型：
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作者：
HENKE, C;FIEGEL, V;BITTERMAN, P
急性肺损伤（ALI）后的生存取决于肺泡的迅速修复，这一过程经常被肺泡腔内肉芽组织的发展所破坏。肺泡内肉芽组织的免疫组织化学检查证实，毛细血管以及肌成纤维细胞的主要细胞成分。因此，我们假设血管生成因子将存在于ALI后的空气-肺界面。为了评估这一假设，通过其诱导内皮细胞迁移的能力来检测来自ALI患者（n = 25）和患者对照（n = 8）的支气管肺泡灌洗液的血管生成生物活性。对照组的灌洗液没有生物活性，而72%的ALI患者的灌洗液促进了内皮细胞迁移。肝素亲和、离子交换和凝胶过滤色谱法将生物活性分解为至少两个部分。其中一个与充分表征的内皮细胞生长因子碱性成纤维细胞生长因子相同。另一个是150 kD的非肝素结合蛋白，其在体外介导内皮细胞迁移和附着，以及在体内介导新血管的生长。这些数据是一致的假设，即毛细血管的生长到肺泡空气中的结果，从血管生成因子存在于肺泡表面的肺后ALI。
Survival after acute lung injury (ALI) depends on prompt alveolar repair, a process frequently subverted by the development of granulation tissue within the alveolar airspace. Immunohistochemical examination of the intraalveolar granulation tissue confirmed that capillaries as well as myofibroblasts were the principal cellular constituents. We therefore hypothesized that angiogenesis factors would be present on the air-lung interface after ALI. To evaluate this hypothesis, bronchoalveolar lavage fluid from patients with ALI (n = 25) and patient controls (n = 8) was examined for angiogenesis bioactivity by its ability of induce endothelial cell migration. While lavage fluid from controls had no bioactivity, lavage fluid from 72% of patients with ALI promoted endothelial cell migration. Heparin affinity, ion exchange, and gel filtration chromatography resolved the bioactivity into at least two moieties. One appeared identical to the well characterized endothelial cell growth factor, basic fibroblast growth factor. The other was a 150-kD non-heparin binding protein that mediated endothelial cell migration and attachment in vitro, and the growth of new vessels in vivo. These data are consistent with the hypothesis that the growth of capillaries into the alveolar airspace results from angiogenesis factors present on the alveolar surface of the lung after ALI.