Fibroblast phenotypes in pulmonary fibrosis

SH Phan - American journal of respiratory cell and molecular …, 2003 - search.proquest.com
SH Phan
American journal of respiratory cell and molecular biology, 2003search.proquest.com
A key feature of pulmonary fibrosis is the presence of fibroblasts at sites of active fibrosis. In
fact, the presence of a distinct lesion, termed a" fibroblastic focus," composed of fibroblasts
or fibroblast-like cells clustered together and relatively well-demarcated from surrounding
cells, has been used as part of the histopathologic criteria for the diagnosis of usual
interstitial pneumonitis (UIP), now considered to be synonymous with idiopathic pulmonary
fibrosis (IPF)(1). Furthermore, the presence of such areas of active fibrosis is the most …
A key feature of pulmonary fibrosis is the presence of fibroblasts at sites of active fibrosis. In fact, the presence of a distinct lesion, termed a" fibroblastic focus," composed of fibroblasts or fibroblast-like cells clustered together and relatively well-demarcated from surrounding cells, has been used as part of the histopathologic criteria for the diagnosis of usual interstitial pneumonitis (UIP), now considered to be synonymous with idiopathic pulmonary fibrosis (IPF)(1). Furthermore, the presence of such areas of active fibrosis is the most reliable prognosticator of progressive fibrosis leading to end-stage lung disease and a fatal outcome (2). Finally, there is ample evidence to suggest that the cells in these areas of active fibrosis are the main cellular source for extracellular matrix expression that typifies fibrosis. All these factors argue for a critical role or roles for these cells in the pathogenesis of progressive fibrosis. In fact, the presumed persistence of these cells may be the basis for disease progression instead of resolution, resulting in end-stage lung disease. Hence, understanding the origin of these cells and their functional analysis should uncover key mechanisms involved in the pathogenesis of IPF and other fibrotic diseases. The situation, however, is complicated by evidence showing that these cells, even within the so-called fibroblastic foci, are phenotypically heterogeneous. The relationship, if any, between these various fibroblast phenotypes is unclear but worthy of study because the findings may provide novel insight into the potential origins of these cells and how they emerge de novo in fibrotic lesions. The objective of this section is to briefly review and highlight the evidence for the presence of diverse fibroblast phenotypes, their potential roles in pulmonary fibrosis, their origin (s), the mechanism of their emergence, and their possible fate in the context of disease progression versus resolution.
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