Bleomycin-Induced Pulmonary Fibrosis in Genetically Mast Cell-Deficient WBB6F1-W/Wv Mice and Mechanism of the Suppressive Effect of Tranilast, an Antiallergic Drug Inhibiting Mediator Release from Mast Cells, on Fibrosis

1991 ◽  
Vol 95 (2-3) ◽  
pp. 195-201 ◽  
Author(s):  
Hiroshi Mori ◽  
Kenji Kawada ◽  
Peng Zhang ◽  
Yuki Uesugi ◽  
Osami Sakamoto ◽  
...  
2005 ◽  
Vol 124 (2) ◽  
pp. 453-456 ◽  
Author(s):  
Sven Guhl ◽  
Richard Stefaniak ◽  
Marc Strathmann ◽  
Magda Babina ◽  
Helmut Piazena ◽  
...  

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Misaki Yashima ◽  
Yukine Sato ◽  
Itsuro Kazama

AbstractCaffeine and catechin, contained in coffee and tea, are commonly consumed substances worldwide. Studies revealed their health promoting functions, such as anti-oxidant, anti-cancer and anti-bacterial properties. Additionally, studies also revealed their roles in ameliorating the symptoms of allergic disorders, indicating their anti-allergic properties. In the present study, using the differential-interference contrast (DIC) microscopy, we examined the effects of caffeine and catechin on the degranulation from rat peritoneal mast cells. Both caffeine and catechin dose-dependently decreased the numbers of degranulating mast cells. At concentrations equal to or higher than 25 mM, caffeine and catechin markedly suppressed the numbers of degranulating mast cells. In contrast, at relatively lower concentrations, both substances did not significantly affect the numbers of degranulating mast cells. However, surprisingly enough, low concentrations of catechin (1, 2.5 mM) synergistically enhanced the suppressive effect of 10 mM caffeine on mast cell degranulation. These results provided direct evidence for the first time that caffeine and catechin dose-dependently inhibited the process of exocytosis. At relatively lower concentrations, caffeine or catechin alone did not stabilize mast cells. However, low concentrations of catechin synergistically potentiated the mast cell-stabilizing property of caffeine.


2006 ◽  
Vol 177 (8) ◽  
pp. 4991-4997 ◽  
Author(s):  
Huan-Yuan Chen ◽  
Bhavya B. Sharma ◽  
Lan Yu ◽  
Riaz Zuberi ◽  
I-Chun Weng ◽  
...  

Thorax ◽  
2019 ◽  
Vol 74 (5) ◽  
pp. 455-465 ◽  
Author(s):  
Chiko Shimbori ◽  
Chandak Upagupta ◽  
Pierre-Simon Bellaye ◽  
Ehab A Ayaub ◽  
Seidai Sato ◽  
...  

BackgroundThe role of mast cells accumulating in idiopathic pulmonary fibrosis (IPF) lungs is unknown.ObjectivesWe investigated the effect of fibrotic extracellular matrix (ECM) on mast cells in experimental and human pulmonary fibrosis.ResultsIn IPF lungs, mast cell numbers were increased and correlated with disease severity (control vs 60%<FVC<90%, mean difference=-222.7, 95% CI −386.3 to −59.2, p=0.004; control vs FVC<60%, mean difference=−301.7, 95% CI of difference −474.1 to −129.34, p=0.0001; FVC>90% vs 60%<FVC<90%, mean difference=−189.6, 95% CI of difference −353.1 to −26.03, p=0.017; FVC>90% vs FVC<60%, mean difference=−268.6, 95% CI of difference −441.0 to −96.17, p=0.0007). Plasma tryptase levels were increased in IPF and negatively correlated with FVC (control vs FVC<60%, mean difference=−17.12, 95% CI of difference −30.02 to −4.22, p=0.006: correlation curves R=−0.045, p=0.025). In a transforming growth factor (TGF)-β1-induced pulmonary fibrosis model, chymase-positive and tryptase-positive mast cells accumulated in fibrotic lung. Lung tissue was decellularised and reseeded with bone marrow or peritoneum-derived mast cells; cells on fibrotic ECM released more TGF-β1 compared with normal ECM (active TGF-β1: bone marrow-derived mast cell (BMMC)-DL vs BMMC-TGF-β1 p=0.0005, peritoneal mast cell (PMC)-DL vs PMC-TGF-β1 p=0.0003, total TGF-β1: BMMC-DL vs BMMC-TGF-β1 p=0.013, PMC-DL vs PMC-TGF-β1 p=0.001). Mechanical stretch of lungs caused mast cell degranulation; mast cell stabilisers inhibited degranulation (histamine: cont vs doxantrazole p=0.004, β-hexosaminidase: cont vs doxantrazole, mean difference=1.007, 95% CI of difference 0.2700 to 1.744, p=0.007) and TGF-β1 activation (pSmad2/Smad2: cont vs dox p=0.006). Cromoglycate attenuated pulmonary fibrosis in rats (collagen: phosphate-buffered saline (PBS) vs cromoglycate p=0.036, fibrotic area: PBS vs cromoglycate p=0.031).ConclusionThis study suggests that mast cells may contribute to the progression of pulmonary fibrosis.


2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Claudia S. Miller ◽  
Raymond F. Palmer ◽  
Tania T. Dempsey ◽  
Nicholas A. Ashford ◽  
Lawrence B. Afrin

Abstract Background This paper explores the relationship between chemical intolerance (CI) and mast cell activation syndrome (MCAS). Worldwide observations provide evidence for a two-stage disease process called toxicant-induced loss of tolerance (TILT) as a mechanism for CI. TILT is initiated by a major exposure event or a series of lower-level exposures. Subsequently, affected individuals report that common chemical inhalants, foods, and drugs (i.e., various xenobiotics) trigger multi-system symptoms. Purpose To determine whether MCAS provides a plausible biological mechanism for CI/TILT. Methods Using the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI), we compared patients diagnosed with MCAS (n = 147) to individuals who reported chemical intolerances (CI/TILT) following various exposures (n = 345) and to healthy controls (n = 76). Using ANOVA, we compared QEESI scores across groups. Clinical scores for the MCAS patient group were used to predict CI status using logistic regression. Results More than half (59%) of the MCAS group met criteria for CI. A logistic regression model illustrates that as the likelihood of patients having MCAS increased, their likelihood of having CI/TILT similarly increased, to a near-perfect correspondence at the high ends of the QEESI and clinical MCAS scores. Symptom and intolerance patterns were nearly identical for the CI and MCAS groups. Discussion We present data suggesting that xenobiotic activation of mast cells may underlie CI/TILT. The strikingly similar symptom and intolerance patterns for MCAS and TILT suggest that xenobiotics disrupt mast cells, leading to either or both of these challenging conditions. Faced with patients suffering from complex illness affecting multiple organ systems and fluctuating inflammatory, allergic, and dystrophic symptoms, clinicians can now ask themselves two questions: (1) Could MCAS be at the root of these problems? (2) Could environmental exposures be driving MC activation and mediator release? Increasing our understanding of the connection between TILT and MCs has the potential to expose a new link between environmental exposures and illness, offering new opportunities for improving individual and public health. Conclusion The close correspondence between QEESI scores and symptom patterns for MCAS and TILT patients supports xenobiotic-driven mast cell activation and mediator release (i.e., MCAS) as a plausible unifying biological mechanism for CI/TILT, with profound implications for medicine, public health, and regulatory toxicology.


Author(s):  
R. Courtoy ◽  
L.J. Simar ◽  
J. Christophe

Several chemical compounds induce amine liberation from mast cells but do not necessarily provoque the granule expulsion. For example, poly-dl-lysine induces modifications of the cellular membrane permeability which promotes ion exchange at the level of mast cell granules. Few of them are expulsed but the majority remains in the cytoplasm and appears less dense to the electrons. A cytochemical analysis has been performed to determine the composition of these granules after the polylysine action.We have previously reported that it was possible to demonstrate polyanions on epon thin sections using a cetylpyridinium ferric thiocyanate method. Organic bases are selectively stained with cobalt thiocyanate and the sulfhydryle groups are characterized with a silver methenamine reaction. These techniques permit to reveal the mast cell granule constituents, i.e. heparin, biogenic amines and basic proteins.


Author(s):  
Kenichi Takaya

Mast cell and basophil granules of the vertebrate contain heparin or related sulfated proteoglycans. Histamine is also present in mammalian mast cells and basophils. However, no histamine is detected in mast cell granules of the amphibian or fish, while it is shown in those of reptiles and birds A quantitative x-ray microanalysis of mast cell granules of fresh frozen dried ultrathin sections of the tongue of Wistar rats and tree frogs disclosed high concentrations of sulfur in rat mast cell granules and those of sulfur and magnesium in the tree frog granules. Their concentrations in tree frog mast cell granules were closely correlated (r=0.94).Fresh frozen dried ultrathin sections and fresh air-dried prints of the tree frog tongue and spleen and young red-eared turtle (ca. 6 g) spleen and heart blood were examined by a quantitative energy-dispersive x-ray microanalysis (X-650, Kevex-7000) for the element constituents of the granules of mast cells and basophils. The specimens were observed by transmission electron microscopy (TEM) (80-200 kV) and followed by scanning transmission electron microscopy (STEM) under an analytical electron microscope (X-650) at an acceleration voltage of 40 kV and a specimen current of 0.2 nA. A spot analysis was performed in a STEM mode for 100 s at a specimen current of 2 nA on the mast cell and basophil granules and other areas of the cells. Histamine was examined by the o-phthalaldehyde method.


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