Mast Cells Induce Activation of Human Lung Fibroblasts in Vitro

Garbuzenko, Ekaterina; Berkman, Neville; Puxeddu, Ilaria; Kramer, Mordechai R.; Nagler, Arnon; Levi‐Schaffer, Francesca

doi:10.1080/01902140490517809

Cited by 33 publications

(29 citation statements)

References 39 publications

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“…As compared to the control (fibroblasts alone) and no cell contact (NC) groups, the proliferation of pulmonary fibroblasts was significantly increased in our co-culture with contact (CC) group. These results are in agreement with previous studies in which MCs promoted fibroblast proliferation in vitro (Garbuzenko et al 2004, Foley et al 2011). In addition, our co-culture conditions promoted fibroblast differentiation into myelofibroblasts (increased α-SMA expression), and induced increased production of growth factors (bFGF, TGFβ1) and Type I collagen.…”

Section: Discussionsupporting

confidence: 83%

“…These foci are primarily comprised of pulmonary fibroblasts and myofibroblasts, which differentiate from fibroblasts in the pulmonary interstitium. Both fibroblasts and myofibroblasts predominantly secrete Types I and III collagen, the major components of the ECM.Previous studies of pulmonary fibrosis have emphasized that mast cells (MCs) promoted the formation of tissue fibrosis via their interactions with pulmonary fibroblasts (Garbuzenko et al 2004). In rats with pulmonary fibrosis, investigators have found that MCs aggregate in areas of pulmonary fibroblast hyperplasia.…”

mentioning

confidence: 94%

“…Previous studies of pulmonary fibrosis have emphasized that mast cells (MCs) promoted the formation of tissue fibrosis via their interactions with pulmonary fibroblasts (Garbuzenko et al 2004). In rats with pulmonary fibrosis, investigators have found that MCs aggregate in areas of pulmonary fibroblast hyperplasia.…”

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confidence: 99%

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Mast Cells Induce Rat Pulmonary Fibroblast Proliferation and Differentiation <i>via</i> Direct Cell–Cell Contact

Cheng

Yang

2012

CYTOLOGIA

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SummaryWe investigated whether direct cell-cell contact between mast cells (MCs) and pulmonary fibroblasts (PFs) was important for PF proliferation, differentiation, and function, which are critically involved in the development of idiopathic pulmonary fibrosis. MCs and PFs were isolated from male Wistar rats for 3 experimental conditions: (1) PFs alone (Controls); (2) co-culture and contact (CC) between MCs and PFs; and (3) co-culture and no contact (NC) between MCs and PFs. We monitored PF proliferation using growth curves and MTT assays, evaluated PF expression of α-smooth muscle actin (α-SMA) by immunocytochemistry, and determined the concentrations of bFGF, TGF-β1, and Type I collagen in culture supernatants by ELISA. After 5 days in culture, CC conditions induced a significant increase in PF proliferation compared to the other 2 conditions. No significant difference was observed between the NC and control conditions. CC conditions also induced significantly higher PF expressions of α-SMA, and bFGF, TGF-β1, and Type I collagen production compared to the other 2 conditions. These results suggest that MCs promote both PF proliferation and their differentiation into myofibroblasts via direct cell-cell contact.Key words bFGF, Interstitial pulmonary fibrosis, Mast cells, Pulmonary fibroblasts, TGF-β1, Type I collagen.Idiopathic pulmonary fibrosis is a disease that progresses gradually and may be fatal under certain conditions. Pathologically, IPF is characterized by general interstitial pneumonia with damage to alveolar epithelial cells, fibroblast proliferation, and the deposition of large amounts of extracellular matrix (ECM) in the interstitium (Chilosi et al. 2006). There are currently no effective therapeutic strategies to restrain the development of IPF.Pulmonary fibroblasts play an important role in the synthesis of collagens and the ECM in the pulmonary interstitium. Thus, understanding the biological behaviors of pulmonary fibroblasts will aid in identifying the mechanisms underlying the formation of pulmonary fibrosis (Lawson et al. 2005). In idiopathic pulmonary fibrosis, there are numerous fibroblast foci in pulmonary connective tissues. These foci are primarily comprised of pulmonary fibroblasts and myofibroblasts, which differentiate from fibroblasts in the pulmonary interstitium. Both fibroblasts and myofibroblasts predominantly secrete Types I and III collagen, the major components of the ECM.Previous studies of pulmonary fibrosis have emphasized that mast cells (MCs) promoted the formation of tissue fibrosis via their interactions with pulmonary fibroblasts (Garbuzenko et al. 2004). In rats with pulmonary fibrosis, investigators have found that MCs aggregate in areas of pulmonary fibroblast hyperplasia. In IPF, it has been demonstrated that MCs produce large amounts of basic fibroblast growth factor (bFGF), and MC aggregates with high levels of bFGF expression have been found in regions with ECM deposition and proliferation of smooth muscle cells/myofi-

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Section: Discussionsupporting

confidence: 83%

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confidence: 94%

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Mast Cells Induce Rat Pulmonary Fibroblast Proliferation and Differentiation <i>via</i> Direct Cell–Cell Contact

Cheng

Yang

2012

CYTOLOGIA

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“…Interactions between these two cell types are known to have proinflammatory effects (15)(16)(17), but less is known about mediators involved in tissue remodeling. Matrix metalloproteinases (MMP) are zinc and calcium-dependent proteases that digest most ECM components.…”

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confidence: 99%

Mast Cell-Fibroblast Interactions Induce Matrix Metalloproteinase-9 Release from Fibroblasts: Role for IgE-Mediated Mast Cell Activation

Abel

Vliagoftis

2008

The Journal of Immunology

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Mast cells adhere to fibroblasts, but the biological effects of adhesion are not well understood. We hypothesized that these adhesive interactions are important for tissue remodeling through the release of matrix metalloproteinases (MMP). Murine bone marrow cultured mast cells (BMCMC) were cocultured with NIH-3T3 fibroblasts or murine lung fibroblasts (CCL-206) and supernatants analyzed for MMP-9 release by gelatin zymography. Coculture of BMCMC for 24 h with NIH-3T3 or CCL-206 fibroblasts increased the release of MMP-9 from fibroblasts by 1.7 ± 0.2 and 2.0 ± 0.7-fold, respectively. Coculture of BMCMC and fibroblasts in the presence of IgE increased further MMP-9 release, which was released by fibroblasts. MMP-9 release was dependent on TNF released from IgE activated BMCMC and on adhesive interactions between BMCMC and fibroblasts. Increased MMP-9 release was also p44/42-dependent, as was MMP-9 up-regulation during coculture of fibroblasts with resting BMCMC. Finally, IgE injection into the mouse ear increased MMP-9 content of the ear tissue in the absence of Ag, indicating that IgE-mediated remodeling may play a pathogenic role in allergic conditions even in the absence of exposure to allergens. In conclusion, mast cell-fibroblast interactions induce the release of proteases important for tissue remodeling, such as MMP-9. MMP-9 release was further increased in the presence of IgE during coculture, suggesting a role for mast cell-fibroblast interactions in atopic conditions.

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“…Mast cells also modulate functional activity of fibroblasts. These cells activate skin [1] and pulmonary [2] fibroblasts. During the development of autoprosthesis, the number of mast cell varied insignificantly from 4.37±0.33 to 3.94±0.25 per 0.01 mm 2 unit area.…”

Section: Resultsmentioning

confidence: 98%