Chemokine (C-C motif) ligand 2 mediates direct and indirect fibrotic responses in human and murine cultured fibrocytes

Ekert, Jason E.; Murray, Lynne A.; Das, Anuk; Sheng, Hai; Giles‐Komar, Jill; Rycyzyn, Michael A.

doi:10.1186/1755-1536-4-23

Cited by 63 publications

(52 citation statements)

References 36 publications

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“…Patients with IPF have elevated numbers of fibrocytes in circulation, and increased percentages of fibrocytes predict early mortality (23). Our studies demonstrated that CCL12 recruited fibrocytes in mice via CCR2 (6) and that CCR2 stimulation of fibrocytes increased expression of collagen 1 (5); these findings were confirmed in human studies (24). Taken together, our data show that CCR2-binding chemokines recruit a novel profibrotic cell type and play important roles in cellular activation and differentiation.…”

Section: Ccr2-binding Chemokines and Lung Fibrosis: More Than Just MIsupporting

confidence: 78%

Following the Path of CCL2 from Prostaglandins to Periostin in Lung Fibrosis

Moore

2014

Am J Respir Cell Mol Biol

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Without question, the greatest and most humbling honor of my scientific career was to learn that I was nominated for the American Thoracic Society Recognition Award for Scientific Accomplishments. On the occasion of this award, as I look back on the progress made in the last 15 years, I am pleased by the scientific insights; however, I am also saddened that we still have no internationally recognized efficacious therapy. This perspective will highlight the areas my laboratory has addressed regarding the pathogenesis of idiopathic pulmonary fibrosis in hopes of identifying new therapeutic targets. Clinical RelevanceThis review offers a perspective covering fibrosis research in the last 15 years, highlighting in particular the role of chemokines, eicosanoids, viral infections, and matricellular proteins.

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Section: Ccr2-binding Chemokines and Lung Fibrosis: More Than Just MIsupporting

confidence: 78%

Following the Path of CCL2 from Prostaglandins to Periostin in Lung Fibrosis

Moore

2014

Am J Respir Cell Mol Biol

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“…Consistent with the reported secretory profile of fibrocytes [4], many of these monocyte/macrophage lineage cells also showed high expression levels of growth factors, such as TGF-β1, MCP-1 (Ccl2), and vascular endothelial growth factor (VEGF). Moreover, these cells also expressed receptors for growth factors, such as receptors for SDF-1α (Cxcr4), MCP-1 (Ccr2), and TGF-β1 (Tgfr1), similar to traditionally defined fibrocytes [30,31]. …”

Section: Resultsmentioning

confidence: 99%

Tracking the Elusive Fibrocyte: Identification and Characterization of Collagen‐Producing Hematopoietic Lineage Cells During Murine Wound Healing

et al. 2014

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Fibrocytes are a unique population of circulating cells reported to exhibit characteristics of both hematopoietic and mesenchymal cells, and play an important role in wound healing. However putative fibrocytes have been found to lose expression of hematopoietic surface markers such as CD45 during differentiation, making it difficult to track these cells in vivo with conventional methodologies. In this study, to distinguish hematopoietic and non-hematopoietic cells without surface markers, we took advantage of the gene vav 1, which is expressed solely on hematopoietic cells but not on other cell types, and established a novel transgenic mouse, in which hematopoietic cells are irreversibly labeled with green fluorescent protein (GFP) and non-hematopoietic cells with red fluorescent protein (RFP). Use of single-cell transcriptional analysis in this mouse model revealed two discrete types of collagen I (Col I) expressing cells of hematopoietic lineage recruited into excisional skin wounds. We confirmed this finding on a protein level, with one subset of these Col I synthesizing cells being CD45+ and CD11b+, consistent with the traditional definition of a fibrocyte, while another was CD45− and Cd11b−, representing a previously unidentified population. Both cell types were found to initially peak, then reduce post-healing, consistent with a disappearance from the wound site and not a loss of identifying surface marker expression. Taken together we have unambiguously identified two cells of hematopoietic origin that are recruited to the wound site and deposit collagen, definitively confirming the existence and natural time-course of fibrocytes in cutaneous healing.

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“…Eker et al 35 reported that human fibrocytes express functional CCR2, after using an optimized technique for isolation of fibrocytes from human blood and demonstrating expression of functional CCR2 by a subpopulation of these cells. Signaling through ligand-CCR2 interactions induces the proliferation of human blood fibrocytes, differentiation of fibrocytes into myofibroblasts, production of type I collagen, and a chemotactic response.…”

Section: Discussionmentioning

confidence: 99%

Fibrocytes and Fibrovascular Membrane Formation in Proliferative Diabetic Retinopathy

Tamaki

Usui‐Ouchi

Murakami

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to investigate whether fibrocytes participate in formation of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR).METHODS. Vitreous fluid and FVM samples were obtained during vitrectomy in patients with PDR. Samples from patients with macular hole or epiretinal membrane were used as controls. Vitreous fluid and FVM samples were subjected to immunohistochemical analysis. In addition, cells isolated from the vitreous fluid of PDR and control patients were cultured in serum-free medium. Fibrocytes were identified among these cells by morphological and immunohistochemical analyses. We examined the number of fibrocytes in PDR patients and control patients. Also, the concentrations of monocyte chemoattractant protein-1 (MCP-1), pentraxin3, and serum amyloid P (SAP) in vitreous fluid samples from PDR patients and control patients were determined by enzyme-linked immunosorbent assay.RESULTS. Fibrocytes were observed in the vitreous and FVM samples from PDR patients. Cells cultured from the vitreous samples of PDR patients were spindle shaped and expressed fibrocyte markers. TGF-b1 induced differentiation of these cells into myofibroblasts. The number of fibrocytes was higher in samples from PDR patients than in samples from control patient. The vitreous fluid concentration of MCP-1 was significantly higher in PDR patients than in controls and showed a significant positive correlation with the number of fibrocytes from the vitreous fluid. Vitreous fluid concentrations of pentraxin3 and SAP were also higher in PDR patients than in control patients.CONCLUSIONS. These findings indicate that fibrocytes may be involved in development of the FVM in PDR.

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Chemokine (C-C motif) ligand 2 mediates direct and indirect fibrotic responses in human and murine cultured fibrocytes

Cited by 63 publications

References 36 publications

Following the Path of CCL2 from Prostaglandins to Periostin in Lung Fibrosis

Following the Path of CCL2 from Prostaglandins to Periostin in Lung Fibrosis

Tracking the Elusive Fibrocyte: Identification and Characterization of Collagen‐Producing Hematopoietic Lineage Cells During Murine Wound Healing

Fibrocytes and Fibrovascular Membrane Formation in Proliferative Diabetic Retinopathy

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