Xu Jun, Kisseleva Tatiana
Department of Medicine, University of California, San Diego, CA 92093, USA.
Department of Surgery, University of California, San Diego, CA 92093, USA
Exp Biol Med (Maywood). 2015 Jun;240(6):691-700. doi: 10.1177/1535370215584933. Epub 2015 May 12.
Chronic liver injury often leads to hepatic fibrosis, a condition associated with increased levels of circulating TGF-β1 and lipopolysaccharide, activation of myofibroblasts, and extensive deposition of extracellular matrix, mostly collagen Type I. Hepatic stellate cells are considered to be the major(1) but not the only source of myofibroblasts in the injured liver.(2) Hepatic myofibroblasts may also originate from portal fibroblasts, mesenchymal cells, and fibrocytes.(3) Since the discovery of fibrocytes in 1994 by Dr. Bucala and colleagues, this bone marrow (BM)-derived collagen Type I-producing CD45(+) cells remain the most fascinating cells of the hematopoietic system. Due to the ability to differentiate into collagen Type I producing cells/myofibroblasts, fibrocytes were implicated in the pathogenesis of liver, skin, lung, and kidney fibrosis. However, studies of different organs often contain controversial results on the number of fibrocytes recruited to the site of injury and their biological function. Furthermore, fibrocytes were implicated in the pathogenesis of sepsis and were shown to possess antimicrobial activity. Finally, in response to specific stimuli, fibrocytes can give rise to fully differentiated macrophages, suggesting that in concurrence with the high plasticity of hematopoietic cells, fibrocytes exhibit progenitor properties. Here, we summarize our current understanding of the role of CD45(+)Collagen Type I(+) BM-derived cells in response to fibrogenic liver injury and septicemia and discuss the most recent evidence supporting the critical role of fibrocytes in the mediation of pro-fibrogenic and/or pro-inflammatory responses.
慢性肝损伤常导致肝纤维化，这种病症与循环中转化生长因子-β1和脂多糖水平升高、肌成纤维细胞活化以及细胞外基质（主要是I型胶原）的大量沉积有关。肝星状细胞被认为是受损肝脏中肌成纤维细胞的主要（1）但并非唯一来源。（2）肝肌成纤维细胞也可能源自门周成纤维细胞、间充质细胞和纤维细胞。（3）自1994年布卡拉博士及其同事发现纤维细胞以来，这种源自骨髓（BM）的产生I型胶原的CD45（+）细胞一直是造血系统中最引人关注的细胞。由于能够分化为产生I型胶原的细胞/肌成纤维细胞，纤维细胞被认为与肝、皮肤、肺和肾纤维化的发病机制有关。然而，针对不同器官的研究，在损伤部位募集的纤维细胞数量及其生物学功能方面，往往得出相互矛盾的结果。此外，纤维细胞还被认为与脓毒症的发病机制有关，并被证明具有抗菌活性。最后，在特定刺激下，纤维细胞可分化为完全成熟的巨噬细胞，这表明纤维细胞与造血细胞的高可塑性一致，具有祖细胞特性。在此，我们总结了目前对源自骨髓的CD45（+）I型胶原（+）细胞在应对致纤维化肝损伤和败血症时所起作用的理解，并讨论了支持纤维细胞在介导促纤维化和/或促炎反应中起关键作用的最新证据。
