Martinet Y, Rom W N, Grotendorst G R, Martin G R, Crystal R G
N Engl J Med. 1987 Jul 23;317(4):202-9. doi: 10.1056/NEJM198707233170404.
Idiopathic pulmonary fibrosis is a fibrotic lung disease characterized by an increased number of mesenchymal cells in the alveolar walls. Alveolar macrophages constitutively express low levels of c-sis, the protooncogene coding for the B chain of platelet-derived growth factor, a protein with chemotactic and mitogenic activity toward mesenchymal cells. We therefore hypothesized that alveolar macrophages in patients with idiopathic pulmonary fibrosis may release increased amounts of platelet-derived growth factor, which might help to explain the accumulation of mesenchymal cells and the fibrosis of the lower respiratory tract in the disease. Evaluation of alveolar macrophages recovered from the lungs of patients with idiopathic pulmonary fibrosis demonstrated that these cells spontaneously released four times more platelet-derived growth factor than did alveolar macrophages recovered from normal persons (P less than 0.01). That the platelet-derived growth factor molecules were potentially active was shown by their chemotactic activity for smooth-muscle cells and their ability to act as a "competence" factor for fibroblast growth. These observations suggest the possibility that the accumulation of mesenchymal cells within the alveolar walls in patients with idiopathic pulmonary fibrosis may result partly from the exaggerated release of the potent mitogen platelet-derived growth factor by mononuclear phagocytes in the lower respiratory tract.
特发性肺纤维化是一种纤维化性肺病，其特征是肺泡壁间充质细胞数量增加。肺泡巨噬细胞组成性表达低水平的c-sis，这是一种原癌基因，编码血小板衍生生长因子的B链，该蛋白对间充质细胞具有趋化和促有丝分裂活性。因此，我们推测特发性肺纤维化患者的肺泡巨噬细胞可能释放更多的血小板衍生生长因子，这可能有助于解释该疾病中间充质细胞的积聚和下呼吸道的纤维化。对从特发性肺纤维化患者肺部回收的肺泡巨噬细胞的评估表明，这些细胞自发释放的血小板衍生生长因子比从正常人回收的肺泡巨噬细胞多四倍（P小于0.01）。血小板衍生生长因子分子的潜在活性通过其对平滑肌细胞的趋化活性以及作为成纤维细胞生长的“能力”因子的能力得以体现。这些观察结果提示，特发性肺纤维化患者肺泡壁内间充质细胞的积聚可能部分是由于下呼吸道单核吞噬细胞过度释放强效有丝分裂原血小板衍生生长因子所致。
