Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.
Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.
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DOI：
10.1084/jem.170.3.727
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发表时间：
1989-09-01
期刊：
影响因子：
--
通讯作者：
Greenberg AH
中科院分区：
文献类型：
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作者：
Khalil N;Bereznay O;Sporn M;Greenberg AH
采用博莱霉素诱导的大鼠肺炎症和纤维化模型，研究胶原合成、转化生长因子β (tgf - β)产生和细胞分布之间的关系。气管内给药博莱霉素后2小时内肺总tgf - β升高，7天后达到峰值，水平是对照组的30倍。随后，在21至28 d的反应后期，产量逐渐下降，但持续下降。通过将[3H]脯氨酸掺入博来霉素处理的大鼠肺成纤维细胞外植体测量，tgf - β的峰值水平高于胶原蛋白和非胶原蛋白的最大合成。免疫组化染色模式将TGF- β最初定位于细支气管上皮细胞和上皮下细胞外基质的细胞质中。肺tgf - β水平在第7天达到峰值，与分散在肺泡间质和有组织簇状的巨噬细胞的强烈tgf - β染色一致。在随后的回应过程中。tgf - β主要与细胞增多和组织修复区域的细胞外基质相关，并与最大成纤维细胞胶原合成相吻合。巨噬细胞产生胶原蛋白和tgf - β之间的时空关系表明，tgf - β在肺纤维化的发病机制中即使不是主要作用，也是重要的作用。
A rat model of bleomycin-induced pulmonary inflammation and fibrosis was used to examine the relationship between collagen synthesis and transforming growth factor beta (TGF-beta) production, and cellular distribution. Total lung TGF-beta was elevated within 2 h of intratracheal bleomycin administration and peaked 7 d later at levels 30-fold higher than controls. This was followed by a gradual decline with lower but persistent levels of production in the late phase of the response between 21 and 28 d later. The peak TGF-beta levels preceded the maximum collagen and noncollagen protein synthesis measured by [3H]proline incorporation into lung fibroblast explants of bleomycin- treated rats. The pattern of immunohistochemical staining localized TGF- beta initially in the cytoplasm of bronchiolar epithelium cells and subepithelial extracellular matrix. The peak of lung TGF-beta levels at 7 d coincided with intense TGF-beta staining of macrophages dispersed in the alveolar interstitium and in organized clusters. Later in the course of the response. TGF-beta was primarily associated with extracellular matrix in regions of increased cellularity and tissue repair, and coincided with the maximum fibroblast collagen synthesis. This temporal and spatial relationship between collagen production and TGF-beta production by macrophages suggests an important if not primary role for TGF-beta in the pathogenesis of the pulmonary fibrosis.