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

Pilling, Darrell; Vakil, Varsha; Cox, Nehemiah; Gomer, Richard H.

doi:10.1073/pnas.1507387112

Cited by 105 publications

(114 citation statements)

References 78 publications

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“…[18–21] To determine inflammation, lung injury, and vascular leakage, BAL cell counts, protein content, and SDS-polyacrylamide gel electrophoresis of BAL fluid were done as described previously. [18] The lungs were then inflated with prewarmed OCT (VWR, Radnor, PA), embedded in OCT, frozen on dry ice, and then stored at −80°C.…”

Section: Methodsmentioning

confidence: 99%

Dietary NaCl affects bleomycin-induced lung fibrosis in mice

Chen

Pilling

2017

Experimental Lung Research

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Purpose High levels of NaCl in the diet are associated with both cardiac and renal fibrosis, but whether salt intake affects pulmonary fibrosis has not been examined. Aim of the Study To test the hypothesis that salt intake might affect pulmonary fibrosis. Materials and Methods Mice were fed low, normal, or high salt diets for 2 weeks, and then treated with oropharyngeal bleomycin to induce pulmonary fibrosis, or oropharyngeal saline as a control. Results As determined by collagen staining of lung sections, and protein levels and cell numbers in the bronchoalveolar lavage (BAL) fluid at 21 days after bleomycin, the high salt diet did not exacerbate bleomycin-induced fibrosis, while the low salt diet attenuated fibrosis. For the bleomycin-treated mice, staining of the post-BAL lung sections indicated that compared to the regular salt diet, high salt increased the number of Ly6c-positive macrophages and decreased the number of CD11c and CD206-positive macrophages and dendritic cells. The low salt diet caused bleomycin-induced leukocyte numbers to be similar to control saline-treated mice, but reduced numbers of CD45/collagen-VI positive fibrocytes. In the saline controls, low dietary salt decreased CD11b and CD11c positive cells in lung sections, and high dietary salt increased fibrocytes. Conclusions Together, these data suggest the possibility that a low salt diet might attenuate pulmonary fibrosis.

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Section: Methodsmentioning

confidence: 99%

Dietary NaCl affects bleomycin-induced lung fibrosis in mice

Chen

Pilling

2017

Experimental Lung Research

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“…[6, 7]. IL-4 level is elevated in ILD and asthma lung biopsies and in peripheral blood and synovial fluid in early RA [8, 15, 19, 26].…”

Section: Discussionmentioning

confidence: 99%

Fibrocyte measurement in peripheral blood correlates with number of cultured mature fibrocytes in vitro and is a potential biomarker for interstitial lung disease in Rheumatoid Arthritis

et al. 2017

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Background Interstitial lung disease (ILD) can be a severe extra-articular disease manifestation in Rheumatoid Arthritis (RA). A potential role of fibrocytes in RA associated ILD (RA-ILD) has not previously been described. We present a modified faster method for measuring circulating fibrocytes, without intracellular staining. The results are compared to the traditional culture method, where the number of monocytes that differentiate into mature fibrocytes in vitro are counted. The results are following compared to disease activity in patients with severe asthma, ILD, RA (without diagnosed ILD) and RA with verified ILD (RA-ILD). Method CD45 + CD34 + CD11b + (7-AAD − CD3 − CD19 − CD294 − ) cells were isolated by cell sorting and stained for pro-collagen type 1. Thirty-nine patients (10 RA, 9 ILD and 10 with severe asthma, 10 with RA-ILD) and 10 healthy controls (HC) were included. Current medication, disease activity, pulmonary function test and radiographic data were collected. Circulating fibrocytes were quantified by flow cytometry. Peripheral blood mononuclear cells were isolated and cultured for 5 days and the numbers of mature fibrocytes were counted. Results 90.2% (mean, SD = 1.5%) of the sorted cells were pro-collagen type 1 positive and thereby fulfilled the criteria for being circulating fibrocytes. The ILD and RA-ILD groups had increased levels of circulating fibrocytes compared to HC ( p < 0.05). Levels of circulating fibrocytes correlated overall to number of monocytes that subsequently in vitro differentiated to mature fibrocytes ( r = 0.81, p < 0.001). RA patients with pathologically reduced diffusion capacity for carbon monoxide adjusted for hemoglobin (DLCO c ) in both the RA and in the combined RA + RA-ILD group, had significantly higher levels of both circulating and number of cultured mature fibrocytes (both p < 0.05). In both groups, the level of circulating fibrocytes and number of mature fibrocytes in culture also correlated to a reduction in DLCO c ( r = −0.61 an r = −0.58 both p < 0.05). Conclusions We presented a fast and valid method for measuring circulating fibrocytes using flow cytometry on lysed peripheral blood. Further, we showed for the first time, that the level of circulating fibrocytes correlated with the number of peripheral blood mononuclear cells, that differentiated into mature fibrocytes in vitro. Reduced DLCO c was correlated with high levels of circulating and mature fibrocytes in RA, which have not been reported prev...

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“…Interestingly, aSMA, the myofibroblast marker, increased in expression level from the interior to the exterior of the fibrous capsule. Macrophages in the fibrous capsule have been shown to stain for aSMA [24, 25], and monocytes are known to differentiate into fibroblast-like cells called fibrocytes [60], so it is not possible to definitively distinguish between macrophages and fibroblasts. Future studies are required to delineate the roles of and interactions between macrophages and fibroblasts in the FBR.…”

Section: Discussionmentioning

confidence: 99%

Temporal and spatial distribution of macrophage phenotype markers in the foreign body response to glutaraldehyde-crosslinked gelatin hydrogels

Wang

Nassiri

et al. 2016

Journal of Biomaterials Science, Polymer Edition

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In recent years, macrophage phenotype has emerged as an important determinant of the success or failure of implanted polymeric biomaterials. However, it is not well understood how changes in biomaterials properties affect the foreign body response or macrophage behavior. Because failed attempts at biomaterial degradation by macrophages have been linked to frustrated phagocytosis, a defining feature of the foreign body response, we hypothesized that increased hydrogel crosslinking density (and decreased degradability) would exacerbate the foreign body response. Gelatin hydrogels were crosslinked with glutaraldehyde (0.05%, 0.1%, and 0.3%) and implanted subcutaneously in C57BL/6 mice over the course of 3 weeks. Histological and immunohistochemical analysis was used to characterize fibrous capsule formation and the temporal and spatial distribution of macrophage phenotype markers. Interestingly, changes in hydrogel crosslinking did not affect the thickness of the fibrous capsule surrounding the hydrogels, expression of the pan-macrophage marker F480, expression of three macrophage phenotype markers (iNOS, Arg1, CD163), or expression of the myofibroblast marker aSMA. With respect to temporal changes, the level of expression of the M1 marker (iNOS) remained relatively constant throughout the study, while the M2 markers Arg1 and CD163 increased over time. Expression of these M2 markers was highly correlated with fibrous capsule thickness. Differences in spatial distribution of staining also were noted, with the strongest staining for iNOS at the hydrogel surface and increasing expression of the myofibroblast marker aSMA toward the outer edge of the fibrous capsule. These results confirm previous reports that macrophages in the foreign body response exhibit characteristics of both M1 and M2 phenotypes. Understanding the effects (or lack of effects) of biomaterial properties on the foreign body response and macrophage phenotype may aid in the rational design of biomaterials to integrate with surrounding tissue.

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

Cited by 105 publications

References 78 publications

Dietary NaCl affects bleomycin-induced lung fibrosis in mice

Dietary NaCl affects bleomycin-induced lung fibrosis in mice

Fibrocyte measurement in peripheral blood correlates with number of cultured mature fibrocytes in vitro and is a potential biomarker for interstitial lung disease in Rheumatoid Arthritis

Temporal and spatial distribution of macrophage phenotype markers in the foreign body response to glutaraldehyde-crosslinked gelatin hydrogels

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