Bitterman P B, Rennard S I, Hunninghake G W, Crystal R G
J Clin Invest. 1982 Oct;70(4):806-22. doi: 10.1172/jci110677.
The number of fibroblasts composing the alveolar structures in controlled within narrow limits by a strictly modulated rate of fibroblast replication. One possible source of growth-modulating signals for alveolar fibroblasts is the alveolar macrophage, a member of the mononuclear phagocyte family of cells, which collectively are known to be important sources of growth factors for a variety of target cells. To evaluate the role of alveolar macrophages in the control of alveolar fibroblast replication, macrophages from normal individuals obtained by bronchoalveolar lavage were maintained in suspension culture with and without added stimuli, and supernates were evaluated for fibroblast growth-promoting effect. Supernates from unstimulated macrophages contained no growth factor activity. In marked contrast, supernates from macrophages stimulated with particulates and immune complexes contained a growth factor that caused a significant increase in fibroblast replication rate. Maximum growth factor activity was observed 3-4 h after macrophage stimulation, at a concentration of 1-2 x 10(6) macrophages/ml. The alveolar macrophagederived growth factor eluted from DEAE-cellulose at 0.27 M NaCl at neutral pH had an apparent molecular weight of 18,000, and appeared to be distinct from other characterized growth factors. The alveolar macrophage-derived growth factor stimulated lung fibroblast DNA synthesis within 12 h, with cell division apparent within 48 h. In serum-free culture, the alveolar macrophage-derived growth factor by itself did not promote fibroblast replication, but rather acted as a progression factor causing a synergistic increase in fibroblast replication rate in the presence of competence factors such as fibroblast growth factor or platelet-derived growth factor. These studies suggest that when stimulated, human alveolar macrophages may modulate, in part, the replication rate of alveolar fibroblasts by releasing a growth factor within the alveolar microenvironment.
成纤维细胞复制速率受到严格调控，从而使构成肺泡结构的成纤维细胞数量维持在狭窄范围内。肺泡巨噬细胞是单核吞噬细胞家族的一员，已知其是多种靶细胞生长因子的重要来源，它可能是肺泡成纤维细胞生长调节信号的一个来源。为了评估肺泡巨噬细胞在控制肺泡成纤维细胞复制中的作用，通过支气管肺泡灌洗从正常个体获取的巨噬细胞在有无添加刺激物的情况下进行悬浮培养，并对培养上清液的成纤维细胞生长促进作用进行评估。未刺激的巨噬细胞培养上清液不含生长因子活性。与之形成显著对比的是，用颗粒和免疫复合物刺激的巨噬细胞培养上清液含有一种生长因子，可使成纤维细胞复制速率显著增加。巨噬细胞刺激后3 - 4小时观察到最大生长因子活性，此时巨噬细胞浓度为1 - 2×10⁶个/毫升。从中性pH值下0.27M NaCl的DEAE - 纤维素柱上洗脱的肺泡巨噬细胞衍生生长因子，其表观分子量为18,000，似乎与其他已鉴定的生长因子不同。肺泡巨噬细胞衍生生长因子在12小时内刺激肺成纤维细胞DNA合成，48小时内可见细胞分裂。在无血清培养中，肺泡巨噬细胞衍生生长因子本身并不促进成纤维细胞复制，而是作为一种促进因子，在存在诸如成纤维细胞生长因子或血小板衍生生长因子等启动因子的情况下，协同增加成纤维细胞复制速率。这些研究表明，受到刺激时，人肺泡巨噬细胞可能通过在肺泡微环境中释放一种生长因子，部分调节肺泡成纤维细胞的复制速率。
