Extracellular matrix remodelling properties of human fibrocytes

Abstract

The fibrocytes are thought to serve as a source of newly deposited collagens I and III during reparative processes and in certain fibrotic disorders, but their matrix remodelling properties are incompletely understood. We evaluated their ability to produce several extracellular matrix (ECM) components, in comparison with fibroblasts, and to participate in collagen turnover. The collagen gene expression profile of fibrocytes differed from that of fibroblasts because fibrocytes constitutively expressed relatively high levels of the mRNA encoding collagen VI and significantly lower levels of the mRNA encoding collagens I, III and V. The proteoglycan (PG) gene expression profile was also different in fibrocytes and fibroblasts because fibrocytes constitutively expressed the mRNA encoding perlecan and versican at relatively high levels and the mRNA encoding biglycan and decorin at low and very low levels, respectively. Moreover, fibrocytes expressed the mRNA for hyaluronan synthase 2 at higher level than fibroblasts. Significant differences between the two cell populations were also demonstrated by metabolic labelling and analysis of the secreted collagenous proteins, PGs and hyaluronan. Fibrocytes constitutively expressed the scavenger receptors CD163 and CD204 as well as the mannose receptors CD206 and Endo180, and internalized and degraded collagen fragments through an Endo180-mediated mechanism. The results of this study demonstrate that human fibrocytes exhibit ECM remodelling properties previously unexplored, including the ability to participate in collagen turnover. The observed differences in collagen and PG expression profile between fibrocytes and fibroblasts suggest that fibrocytes may predominantly have a matrix-stabilizing function.

Interactions between the Bronchial Epithelium and Fibrocytes in the Pathogenesis of Airway Remodeling in Asthma

“…In healthy individuals, the frequency of authentic mature fibrocytes (cells that uniquely co-express CD34, CD45RO, COL1 mRNA and COL1 protein) in the peripheral blood is very low, with numbers ranging from 1400 to 8200/ml [32]. This fact explains why it is possible to obtain a sufficient number of normal fibrocytes for in-vitro testing solely in long-term cultures of peripheral blood mononuclear cells which selectively favor the proliferation, differentiation and survival of this cell population [35,36]. By contrast, there is a marked increase in the number of peripheral blood fibrocytes in patients with allergen-exacerbated asthma or chronically severe, treatment-refractory disease [31,32,37,39].…”

“…It is worth noting that the collagen and proteoglycan gene expression profile of fibrocytes would suggest that the main function of fibrocytes is tissue stabilization [36]. Thus, the fibrotic changes specifically induced by fibrocytes and the contractile force generated by -SMA+ fibrocytes in the subepithelial zone may concur to prevent further structural damage during repeated episodes of bronchial constriction in transiently uncontrolled or treatment-refractory asthma by enhancing the resistance to mechanical stress of an epithelial barrier weakened by the chronic inflammatory process [36,60,61] (Fig.…”

Fibrocytes in Scleroderma Lung Fibrosis

“…However, because CD34 is frequently lost upon entry into target tissue Phillips et al, 2004) its absence does not rule out a cell as being a fibrocyte. Fibrocytes also produce a wide array of ECM components (Bianchetti et al, 2011;Bellini & Mattoli, 2007;Pilling et al, 2009). A listing of fibrocyte markers is shown in Table 1.…”

Pathogenetic and prognostic roles of bloodborne fibrocytes in asthma

“…These cells can exhibit predominant proinflammatory activities or predominant profibrotic properties at tissue sites, depending on the host's response to diverse environmental insults (allergens, viruses, irritants) (Isgrò et al, 2013b) and on the characteristics of the local cell infiltrate and cytokine milieu (Bellini et al, 2012;Sazuka et al, 2014). Similarly to other cells with combined antigenpresenting function and mesenchymal cell-like features (Muñoz-Fernández et al, 2006;Saada et al, 2006), they acquire a myofibroblast-like phenotype in vitro and at the tissue sites because of the expression of adhesion molecules also present on the surface of these cells (Bianchetti et al, 2012b) and the inducible synthesis of the intracellular contractile protein α-smooth muscle actin (α-SMA) (Abe et al, 2001;Schmidt et al, 2003;Mori et al, 2005;Saunders et al, 2009).…”

“…Fcs have antigen-presenting function (Chesney et al, 1997;Isgrò et al, 2013b) and proinflammatory activities (Chesney et al, 1998;Bellini et al, 2012;Isgrò et al, 2013a;2013b) relevant to asthma (Mattoli, 2015). They participate in extracellular matrix (EM) remodeling through the production of some of the collagens and noncollagenous EM components synthesized in larger quantities by fibroblasts (Bucala et al, 1994;Chesney et al, 1998;Abe et al, 2001;Bianchetti et al, 2012b), and are also involved in collagen uptake and degradation (Bianchetti et al, 2012b). These cells can exhibit predominant proinflammatory activities or predominant profibrotic properties at tissue sites, depending on the host's response to diverse environmental insults (allergens, viruses, irritants) (Isgrò et al, 2013b) and on the characteristics of the local cell infiltrate and cytokine milieu (Bellini et al, 2012;Sazuka et al, 2014).…”