Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease

Mehrad, Borna; Burdick, Marie D.; Zisman, David A.; Keane, Michael P.; Belperio, John A.; Strieter, Robert M.

doi:10.1016/j.bbrc.2006.11.149

Cited by 234 publications

(246 citation statements)

References 23 publications

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“…Fibrocytes are rare in normal heart, lung, and liver, whereas fibrocytes are readily detected in fibrotic lesions in these tissues (3,10,(16)(17)(18)(19). Fibrocytes play a key role in wound healing and fibrosis, and in agreement with our observation that lumican promotes fibrocyte differentiation, lumican knockout mice have poor wound healing and are resistant to carbon tetrachloride-induced liver fibrosis (3,47,64).…”

Section: Discussionsupporting

confidence: 85%

“…Fibrocytes are also found in the scar tissue-like lesions associated with fibrotic diseases such as pulmonary fibrosis, congestive heart failure, cirrhosis of the liver, and nephrogenic systemic fibrosis (3,(7)(8)(9)(10)(11). Fibrocytes express markers of both hematopoietic cells (CD34, CD45, FcγR, LSP-1, MHC class II) and stromal cells (collagens, fibronectin, and matrix metalloproteases) (2,3,(12)(13)(14).…”

mentioning

confidence: 99%

“…Fibrocytes also promote angiogenesis by secreting VEGF, bFGF, IL-8, and PDGF (15). A key question about fibrocyte differentiation and fibrosis is why fibrocytes are readily observed in fibrotic lesions, but are rarely observed in healthy tissues (3,10,(16)(17)(18)(19).…”

mentioning

confidence: 99%

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TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

Pilling

Vakil

Cox

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

114

103

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In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived fibroblast-like cells called fibrocytes help to form scar tissue. Although fibrocytes promote collagen production by fibroblasts, little is known about signaling from fibroblasts to fibrocytes. In this report, we show that fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that lumican, but not the related proteoglycan decorin, promotes human fibrocyte differentiation. Lumican competes with the serum fibrocyte differentiation inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors that affect fibrocyte differentiation, lumican has no detectable effect on macrophage differentiation or polarization. α2β1, αMβ2, and αXβ2 integrins are needed for lumican-induced fibrocyte differentiation. In lung tissue from pulmonary fibrosis patients with relatively normal lung function, lumican is present at low levels throughout the tissue, whereas patients with advanced disease have pronounced lumican expression in the fibrotic lesions. These data may explain why fibrocytes are increased in fibrotic tissues, suggest that the levels of lumican in tissues may have a significant effect on the decision of monocytes to differentiate into fibrocytes, and indicate that modulating lumican signaling may be useful as a therapeutic for fibrosis.

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Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

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TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

Pilling

Vakil

Cox

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

114

103

View full text Add to dashboard Cite

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“…Fibrocytes have been implicated in fibrotic airways diseases, such as interstitial lung diseases and particularly in pulmonary fibrosis (PF) [63], and have been suggested as a biomarker for idiopathic pulmonary fibrosis (IPF) severity [64]. ECM deposition by fibrocytes and fibroblasts are regulated during normal wound repair [65].…”

Section: Fibrocytesmentioning

confidence: 99%

Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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In chronic lung disorders such as in asthma and chronic obstructive pulmonary disease (COPD) there is increased bronchial angiogenesis and remodelling of pulmonary vessels culminating to altered bronchial and pulmonary circulation. The involvement of residential cells such as endothelial cells, smooth muscle cells and pulmonary fibroblasts, all appear to have a crucial role in the progression of vascular inflammation and remodelling. The regulatory abnormalities, growth factors and mediators implicated in the pulmonary vascular changes of asthma and COPD subjects and potential therapeutic targets have been described in this review.

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“…Fibrocytes are also found in lesions associated with fibrotic diseases such as pulmonary fibrosis, congestive heart failure, cirrhosis of the liver, and nephrogenic systemic fibrosis (3,(5)(6)(7)(8)(9). Fibrocytes express markers of both hematopoietic cells (CD34, CD45, FcγR, LSP-1, and MHC class II) and stromal cells (collagens, fibronectin, and matrix metalloproteases) (2,3,(10)(11)(12).…”

mentioning

confidence: 99%

Fibroblasts secrete Slit2 to inhibit fibrocyte differentiation and fibrosis

Pilling

Zheng

Vakil

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance A key question in fibrosing diseases is why monocytes do not become fibrocytes in healthy tissues but can become fibrocytes in fibrotic lesions. We show that fibroblasts secrete a signal that inhibits the differentiation of monocytes into fibrocytes. We identify the signal as Slit2 and show that Slit2 levels are low in fibrotic lesions. We also show that injection of Slit2 prevents fibrosis in a mouse model of lung fibrosis. The identification of Slit2 as a key signal in normal tissues that prevents entering monocytes from becoming fibrocytes represents a major advance in our understanding of the regulation of the innate immune system and how fibrosis propagates, as well as a potential novel therapeutic for fibrosis.

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Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease

Cited by 234 publications

References 23 publications

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

Pulmonary vascular changes in asthma and COPD

Fibroblasts secrete Slit2 to inhibit fibrocyte differentiation and fibrosis

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