Macrophage production of basic fibroblast growth factor in the fibroproliferative disorder of alveolar fibrosis after lung injury.
Macrophage production of basic fibroblast growth factor in the fibroproliferative disorder of alveolar fibrosis after lung injury.
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发表时间：
1993-10
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通讯作者：
C. Henke;William Marineili;J. Jessurun;Joan Fox;Dana J. Harms;M. Peterson;Chiang Lan;Paul Doran
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作者：
C. Henke;William Marineili;J. Jessurun;Joan Fox;Dana J. Harms;M. Peterson;Chiang Lan;Paul Doran
在损伤后的器官修复中，巨噬细胞聚集，由成纤维细胞和内皮细胞组成的肉芽组织在损伤区域发育。碱性成纤维细胞生长因子是成纤维细胞和内皮细胞生长的有力刺激因子，与成纤维细胞的增殖过程有关。巨噬细胞被认为在纤维增殖反应中发挥核心作用，先前的研究表明它们产生碱性成纤维细胞生长因子。虽然巨噬细胞在纤维增殖过程中产生碱性成纤维细胞生长因子似乎是合理的，但目前还没有数据直接确定巨噬细胞是纤维增生性疾病中碱性成纤维细胞生长因子的来源。我们使用肺损伤后急性肺泡内肉芽组织形成的模型来确定巨噬细胞是否是自然发生的纤维增殖过程中碱性成纤维细胞生长因子的细胞来源。为了验证这一假设，严重急性肺损伤患者在肺修复阶段接受了支气管肺泡灌洗。聚合酶链式反应和Northern分析表明，巨噬细胞中存在两种bFGF信使RNA(4.4kb和1.9kb)。对回收的巨噬细胞的代谢标记研究显示，新合成的18kd蛋白与bFGF的抗原性相似。对急性肺损伤后死亡患者肺组织的免疫组织化学评估显示，在含有成纤维细胞和血管组织增殖的空气中存在大量bFGF免疫反应的巨噬细胞。在急性肺损伤后肺泡内纤维化的纤维增生性疾病中，肺泡巨噬细胞是碱性成纤维细胞生长因子的细胞来源。
In organ repair following injury, macrophages accumulate and granulation tissue, comprised of fibroblasts and endothelial cells, develops in the injured area. Basic fibroblast growth factor (bFGF), a potent stimulator of fibroblast and endothelial cell growth, has been linked to the fibroproliferative process. Macrophages are thought to play a central role in the fibroproliferative response, and prior studies indicate that they produce bFGF. Whereas it is plausible that macrophages produce bFGF in a fibroproliferative process, currently no data exists that directly identifies the macrophage as a source of bFGF in a fibroproliferative disorder. We used the model of acute intraalveolar granulation tissue formation following lung injury to determine if the macrophage was a cellular source of bFGF in a naturally occurring fibroproliferative process. To examine this hypothesis, patients with severe acute lung injury underwent bronchoalveolar lavage during the phase of lung repair. Polymerase chain reaction and Northern analysis of macrophage RNA revealed the presence of two species of bFGF messenger RNA (4.4 kb and 1.9 kb). Metabolic labeling studies of recovered macrophages revealed a newly synthesized 18-kd protein with antigenic similarity to bFGF. Immunohistochemical evaluation of lung tissue from patients who died following acute lung injury, showed numerous bFGF immunoreactive macrophages present within airspaces containing fibroblastic and vascular tissue proliferation. This investigation has identified the alveolar macrophage as a cellular source of bFGF in the fibroproliferative disorder of intraalveolar fibrosis following acute lung injury.