scholarly journals Role of Mast Cell Tryptase in Renal Interstitial Fibrosis

2001 ◽  
Vol 12 (8) ◽  
pp. 1668-1676 ◽  
Author(s):  
SHUJI KONDO ◽  
SHOJI KAGAMI ◽  
HIROSHI KIDO ◽  
FRANK STRUTZ ◽  
GERHARD A. MÜLLER ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mast Cell ◽  
Mast Cells ◽  
Dna Synthesis ◽  
Interstitial Fibrosis ◽  
Renal Diseases ◽  
Type I ◽  
Mast Cell Tryptase ◽  
Renal Interstitial Fibrosis

Abstract. Renal interstitial fibrosis is characterized by increased proliferation of fibroblasts and excessive accumulation of extracellular matrix. Mast cell tryptase has been implicated in the development of tissue fibrosis in skin and lungs. However, the significance of mast cell tryptase in human renal diseases has not been investigated. The potential role of mast cell-derived tryptase in the development of renal fibrosis was studied using immunohistochemical techniques and cultured human renal fibroblast cell lines. Semiquantitative immunostaining analysis of samples from 70 patients with several renal diseases, including IgA glomerulonephritis (GN) (n = 30), non-IgA GN (n = 5), membranous GN (n = 5), focal segmental glomerulosclerosis (n = 4), minor glomerular abnormalities (n = 5), lupus nephritis (n = 3), and acute or chronic tubulointerstitial nephritis (n = 18), revealed that the degree of renal interstitial fibrosis was well correlated with the number of infiltrating tryptase-positive mast cells (P < 0.01). Mast cells could not be detected in damaged glomeruli in any form of renal disease. [3H]Thymidine uptake experiments demonstrated that DNA synthesis by cultured renal fibroblasts was increased with the concentration of tryptase (0.5 to 5 nM) coincubated with heparin and was suppressed by coincubation with the protease inhibitors leupeptin and benzamidine hydrochloride. Tryptase alone also increased DNA synthesis by fibroblasts but exhibited less effectiveness, compared with the combination of tryptase and heparin. Conversely, heparin alone suppressed DNA synthesis by fibroblasts. Metabolic [35S]methionine-labeling experiments with cultured renal fibroblasts indicated that tryptase increased the synthesis of fibronectin and collagen type I, in a dose-dependent manner. These findings suggest that mast cell tryptase plays a role in the proliferation and extracellular matrix protein production of renal interstitial fibroblasts and thus contributes to the development of renal interstitial fibrosis.

scholarly journals Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis

2016 ◽  
Vol 11 ◽  
pp. BMI.S38439 ◽  
Author(s):  
Federica Genovese ◽  
Zsolt S. Kàrpàti ◽  
Signe H. Nielsen ◽  
Morten A. Karsdal
Keyword(s):  
Extracellular Matrix ◽  
Collagen Type ◽  
Interstitial Fibrosis ◽  
Ex Vivo ◽  
Collagen Type I ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Renal Interstitial Fibrosis ◽  
Ex Vivo Model

The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) surgery of the right ureter. The left kidney (contralateral) was used as internal control. Six rats were sham operated and used as the control group. Rats were terminated two weeks after the surgery; the kidneys were excised and precision-cut kidney slices (PCKSs) were cultured for five days in serum-free medium. Markers of collagen type I formation (P1NP), collagen type I and III degradation (C1M and C3M), and α-smooth muscle actin (αSMA) were measured in the PCKS supernatants by enzyme-linked immunosorbent assay. P1NP, C1M, C3M, and α-SMA were increased up to 2- to 13-fold in supernatants of tissue slices from the UUO-ligated kidneys compared with the contralateral kidneys ( P < 0.001) and with the kidneys of sham-operated animals ( P < 0.0001). The markers could also reflect the level of fibrosis in different animals. The UUO PCKS ex vivo model provides a valuable translational tool for investigating the extracellular matrix remodeling associated with renal interstitial fibrosis.

Mass cells contribute to O3-induced epithelial damage and proliferation in nasal and bronchial airways of mice

1996 ◽  
Vol 80 (4) ◽  
pp. 1322-1330 ◽  
Author(s):  
M. Longphre ◽  
L. Y. Zhang ◽  
J. R. Harkema ◽  
S. R. Kleeberger
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Dna Synthesis ◽  
Measured Parameter ◽  
Epithelial Injury ◽  
Epithelial Damage ◽  
Proinflammatory Mediators ◽  
Cell Counts ◽  
Air Control

Ozone (O3) exposure produces inflammation in the airways of humans and animal models. However, the mechanism by which O3 affects these changes is uncertain. Mast cells are strategically located below the epithelium of the airways and are capable of releasing a number of proinflammatory mediators. We tested the hypothesis that mast cells contribute to inflammation, epithelial sloughing, and epithelial proliferation in the nasal and terminal bronchiolar murine airways after O3 exposure. Mast cell-sufficient (+/+), mast cell-deficient (W/Wv), and mast cell-repleted [bone marrow-transplanted (BMT) W/Wv] mice were exposed to 2 ppm O3 or filtered air for 3 h. Nasal and bronchoalveolar lavage fluids were collected 6 and 24 h after exposure. Differential cell counts and protein content of the lavage fluids were used as indicators of inflammation and permeability changes in the airways. O3-induced epithelial injury was assessed by light microscopy, and O3-induced DNA synthesis in airway epithelium was estimated by using a 5-bromo-2′-deoxyuridine-labeling index in the nasal and terminal bronchiolar epithelia. Relative to air control mice, O3 caused significant increases in inflammation, epithelial injury, and epithelial DNA synthesis in +/+ mice. There was no significant effect of O3 exposure on any measured parameter in the W/Wv mice. To further assess the role of mast cells in O3-induced epithelial damage, mast cells were restored in W/Wv mice by BMT from +/+ congeners. Relative to sham-transplanted W/Wv mice, O3 caused significant increases in epithelial damage and DNA synthesis as well as inflammatory indicators in BMT W/Wv mice. These observations are consistent with the hypothesis that mast cells significantly modulate the inflammatory and proliferative responses of the murine airways to O3.

scholarly journals Anti-inflammatory and pro-resolving role of mast cells during resolution of local inflammation.

2021 ◽  
Author(s):  
◽  
Lisa Kornstädt
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
The Body ◽  
Type I ◽  
Local Inflammation ◽  
Ontology Term ◽  
Resolution Of Inflammation ◽  
Macrophage Phagocytosis ◽  
Anti Inflammatory

Mast cells are long-lived tissue-resident leukocytes, located most abundantly in the skin and mucosal surfaces. They belong to the first line of defence of the body, protecting against invading pathogens, toxins and allergens. Their secretory granules are densely packed with a plethora of mediators, which can be released immediately upon activation of the cell. Next to their role in IgE-mediated allergic diseases and in promoting inflammation, potential anti-inflammatory functions have been assigned to mast cells, depending on the biological setting. The aim of this thesis was to contribute to a better understanding of the role of mast cells during the resolution of a local inflammation. Therefore, in a first of step a suitable model of a local inflammation had to be identified. Since comparison of the two Toll-like receptor (TLR)-agonists zymosan and lipopolysaccharide (LPS), which are most commonly used to locally induce inflammation, revealed a systemic response after LPS-injection and a local inflammation after zymosan-injection, the TLR2 agonist zymosan was chosen for the subsequent experiments. Multi epitope ligand cartography (MELC) combined with statistical neighbourhood analysis showed that mast cells are located in an anti-inflammatory microenvironment next to M2 macrophages during resolution of inflammation, while neutrophils and M1 macrophages are located in the zymosan-filled core of the inflammation. Furthermore, infiltrating neutrophils during peak inflammation and an increasing population of macrophages phagocytosing neutrophils during resolution of inflammation could be observed. MELC as well as flow cytometry analysis of mast cell-deficient mice revealed a decreased phagocytosing activity of macrophages in the absence of mast cells. As an untargeted approach to identify mast cell-derived mediators induced by zymosan, mRNA sequencing of bone marrow-derived mast cells (BMMCs) was performed. Gene ontology term analysis of the sequencing data revealed the induction of the type I interferon (IFN) pathway as the dominant response. Contradicting previous studies, I could validate the production of IFN-β by mast cells in response to zymosan and LPS in vitro. Furthermore IFN-β expression by mast cells was also detected in vivo. In accordance with previous studies regarding other cell types the release of IFN-β by mast cells depends on endosomal signaling. The potential of IFN-β to enhance the phagocytosing activity of macrophages has been demonstrated recently. Besides IFN-β, various other mediators with reported enhancing effects on macrophage phagocytosis were also induced by zymosan in BMMCs, including Interleukin (IL)-1β, IL-4, IL-13, and Prostaglandin (PG) E2. Thus, either one of these mediators alone or a combination of them could promote macrophage phagocytosis. In conclusion, I herein present mast cells as a novel source for IFN-β induced by non-viral TLR ligands and demonstrate their enhancing effect on macrophage phagocytosis, thereby contributing to the resolution of inflammation.

scholarly journals The Role of Mast Cell Tryptase in Neoangiogenesis of Premalignant and Malignant Lesions of the Uterine Cervix

2001 ◽  
Vol 49 (8) ◽  
pp. 1061-1062 ◽  
Author(s):  
L. Benítez–Bribiesca ◽  
A. Wong ◽  
D. Utrera ◽  
E. Castellanos
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Uterine Cervix ◽  
Linear Increase ◽  
Vascular Endothelial ◽  
Mast Cell Tryptase ◽  
Malignant Lesions ◽  
Safranin O ◽  
Endothelial Growth Factors

Recently, mast cell tryptase has been identified as another potent proangiogenic factor in tumors, along with fibroblast and vascular endothelial growth factors. Its role has been studied in a number of cancers, including carcinoma of the uterine cervix, with discordant results. Our aim was to study the expression of tryptase and bFGF in mast cells (MCs) during development of neoangiogenesis in premalignant and malignant lesions of the cervix. Biopsy specimens from 21 patients without cancer and from 63 patients with dysplasias and squamous cell carcinomas were used. They were stained with Alcian blue– safranin O (ABSO) and immunostained with specific antibodies against factor VIII, CD105, tryptase, and bFGF. Tryptase-positive mast cells increased with tumor progression and were close to newly formed blood vessels. Vascularization showed a linear increase from dysplasia to invasive cancer. We suggest that MC tryptase may upregulate neoangiogenesis in carcinogenesis of the uterine cervix. (J Histochem Cytochem 49:1061–1062, 2001)

scholarly journals The role of mast cells in accelerating our skin aging

2021 ◽  
Vol 2 (5) ◽  
Author(s):  
Sara Mohamed Naguib Abdel Hafez ◽  
◽  
El Shimaa MN Ali ◽  
Salsabil Mohamed Naguib ◽  
◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mast Cell ◽  
Mast Cells ◽  
Aging Process ◽  
Recent Decade ◽  
The Elderly ◽  
Medical Problem ◽  
Skin Aging ◽  
Skin Damage

Everyone wishes to appear younger. Actually, women spend a lot of efforts and money to fight aging appearance of skin. In the recent decade, skin aging has become an annoying social and medical problem at the levels of modern societies. Unfortunately, up to now, scientists have not discovered an effective treatment to overcome the appearance of the elderly skin. Although, researchers try hard to discover the main causes and mechanisms of getting skin more aged to earn a youthful look for skin appearance, some researchers suggested that mast cells (MCSs) were scarcely found neither in fetus dermis nor the youth while they are clearly detected in dermis of senile people which proposes the function of these cells in controlling the process of skin caducity. Researchers have taken into consideration the beneficial effect of MCS in controlling skin caducity. Recently, MCS is considered as an effective route in treatment elderly skin. Non-synthetic products can inhibit MCS activation so considered as a good functional ingredient fighting skin aging process as this cell implicated in skin damage and aging; degranulation of papillary dermal MCS might result in inflammation, reconstruction of extracellular matrix and angiogenesis with subsequently induced skin caducity. This mini review summarizes the crucial role of activated MCS in the dermal aging process. Keywords: skin; aging; mast cell.

The role of mast cells and mast cell tryptase in skin tags: an immunohistochemical study

2015 ◽  
Vol 28 (2) ◽  
pp. 355
Author(s):  
ShimaaF Seif El Naser ◽  
AlaaH Maraee ◽  
AsmaaG Abdou
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunohistochemical Study ◽  
Mast Cell Tryptase ◽  
Skin Tags

scholarly journals The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cell Metabolism ◽  
Breast Tumors ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Desmoplastic Reaction ◽  
The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

Comparative analysis of the role of mast cells in murine asthma models using Kit‐sufficient mast cell‐deficient animals

Allergy ◽  
2021 ◽  
Author(s):  
Lea Pohlmeier ◽  
Sanchaita Sriwal Sonar ◽  
Hans‐Reimer Rodewald ◽  
Manfred Kopf ◽  
Luigi Tortola
Keyword(s):  
Mast Cell ◽  
Comparative Analysis ◽  
Mast Cells

Mast cell heterogeneity

1984 ◽  
Vol 62 (6) ◽  
pp. 734-737 ◽  
Author(s):  
F. Shanahan ◽  
J. A. Denburg ◽  
J. Bienenstock ◽  
A. D. Befus
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Regulatory Peptides ◽  
Cell Heterogeneity ◽  
Cell Secretion ◽  
Biochemical Basis ◽  
Mucosal Mast Cells ◽  
Mast Cell Heterogeneity

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell sub-populations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.

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