Fibrocytes and progression of fibrotic lung disease. Ready for showtime?
Fibrocytes and progression of fibrotic lung disease. Ready for showtime?
复制标题
纤维细胞和纤维化肺病的进展。
DOI：
10.1164/rccm.201411-2013ed
复制
发表时间：
2014
影响因子：
24.7
通讯作者：
Kolb,Martin
中科院分区：
文献类型：
--
作者：
Moore,BethanyB;Kolb,Martin
Hermansky-Pudlak syndrome (HPS) is group of autosomal recessive disorders, of which three subtypes, HPS-1, HPS-2, and HPS-4, reproducibly result in interstitial lung disease (ILD)(1). The nature of the hereditary mutation allows ILD to develop at much younger ages than seen in idiopathic pulmonary fibrosis (IPF), and the corresponding presence of albinism in these patients allows a unique opportunity to identify patients at very high risk of developing lung fibrosis before the disease process is well established. In this issue of the Journal, Trimble and colleagues (pp. 1395–1401) studied a group of 65 patients with HPS to correlate circulating fibrocytes with measures of lung fibrosis in a cross-sectional and longitudinal analysis (2). They found that patients with HPS with ILD had elevated numbers of fibrocytes in their circulation when compared with patients with HPS without ILD or with normal control patients. Interestingly, the increased fibrocytes seen in patients with ILD were driven by a subset of patients with very high counts (n= z10). This is reminiscent of previous findings in IPF, in which a subset of patients with IPF also had high circulating fibrocyte levels, which was predictive for patients at risk for acute exacerbation and death (3). In the current study looking at patients with HPS, only those with ILD demonstrated the presence of activated fibrocytes, defined by expression of a-smooth muscle actin (a-SMA). Another major finding of this study was an analysis that demonstrated that patients with HPS with absolute circulating fibrocyte counts above 3.35 3 105 cells/ml were more likely to die before their next visit (which occurred at a mean time of 347 d later). Similarly, patients who had a fibrocyte count of 1 3 106 cells/ml at any time were also more likely to die during the study period. Interestingly, however, higher fibrocyte counts did not necessarily predict declines in lung function (forced vital capacity or diffusion capacity for carbon monoxide), results that also mirror previous findings in IPF (3). In the last decade, fibrocytes have received interest as a potential blood biomarker that can predict disease severity or disease progression in ILD, including IPF (3) and systemic sclerosis–associated ILD (4, 5). Fibrocytes are circulating bone marrow–derived mesenchymal cell progenitors that can differentiate into fibroblasts and myofibroblasts once they enter the tissue (6). Fibrocytes are believed to be involved in the disease pathogenesis of several fibrotic disorders affecting lungs, liver, kidneys, and other organs, but their exact biological role is not fully understood. The most commonly used markers to identify fibrocytes are surface expression of CD45, the common leukocyte antigen, and intracellular expression of collagen 1 or pro-collagen 1, markers of mesenchymal cells, although many studies have also examined chemokine receptors and a-SMA. Thus, fibrocytes are phenotypically cells of hematopoietic origin that coexpress markers of mesenchymal cells. Many groups studying the role of fibrocytes in the pathogenesis of fibrosis or investigating them as biomarkers of disease progression (such as Trimble and colleagues [2]) use different marker sets and also handle the samples differently, which likely explains the variability and sometimes inconsistency of reports. Several human studies and animal models have demonstrated increased fibrocytes in the lungs or circulation (reviewed in Reference 7), confirming that they participate in fibrosis. Further, adoptive transfer of fibrocytes can augment experimental fibrosis, suggesting high numbers may be detrimental (8, 9). Because of this and the fact that fibrocytes readily differentiate into fibroblasts in vitro, it …
