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 A Comparative Analysis of Mast Cell Quantification in Five Common Dermatoses: Lichen Simplex Chronicus, Psoriasis, Lichen Planus, Lupus, and Insect Bite/Allergic Contact Dermatitis/Nummular Dermatitis

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Nikhil Patel ◽  
Amir Mohammadi ◽  
Ronald Rhatigan
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Large Body ◽  
Dendritic Morphology ◽  
Hair Follicles ◽  
The Body ◽  
Tissue Sections ◽  
Lichen Simplex Chronicus ◽  
Allergic Contact

There is a large body of literature demonstrating an important role of mast cells in adaptive and innate immunity. The distribution of mast cells in the skin varies in different parts of the body. It is well known that mast cells are important for effector functions of classic IgE-associated allergic disorders as well as in host defense against infective agents and influence the manifestation of autoimmune diseases. We aimed to quantify mast cells in five common dermatoses and compare them statistically with respect to the immunostains. We retrieved paraffin-embedded tissue sections from the archives of the Pathology Department at the UF, Jacksonville, for five cases with each of the above diagnosis from the last three years. We performed CD-117 and tolidine blue stains on each one of them. The presence or absence of mast cells was evaluated and quantified. We observed that, in the skin, mast cells are mainly located close to the vessels, smooth muscle cells, hair follicles, and nerve ending. Our study showed that the mast cell distribution pattern is different across the two methods of staining for the five aforesaid dermatoses. The other important observation was the dendritic morphology of the mast cells.

scholarly journals Bacterial and Fungal Toll-Like Receptor Activation Elicits Type I IFN Responses in Mast Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Lisa Kornstädt ◽  
Sandra Pierre ◽  
Andreas Weigert ◽  
Stefanie Ebersberger ◽  
Tim J. Schäufele ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Allergic Diseases ◽  
Receptor Activation ◽  
Type I ◽  
Toll Like Receptor ◽  
Resolution Of Inflammation ◽  
Type I Ifns ◽  
Ige Mediated

Next to their role in IgE-mediated allergic diseases and in promoting inflammation, mast cells also have antiinflammatory functions. They release pro- as well as antiinflammatory mediators, depending on the biological setting. Here we aimed to better understand the role of mast cells during the resolution phase of a local inflammation induced with the Toll-like receptor (TLR)-2 agonist zymosan. Multiple sequential immunohistology combined with a statistical neighborhood analysis showed that mast cells are located in a predominantly antiinflammatory microenvironment during resolution of inflammation and that mast cell-deficiency causes decreased efferocytosis in the resolution phase. Accordingly, FACS analysis showed decreased phagocytosis of zymosan and neutrophils by macrophages in mast cell-deficient mice. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which is known to enhance phagocytosis by macrophages. Both, zymosan and lipopolysaccharides (LPS) induced IFN-β synthesis in BMMCs in similar amounts as in bone marrow derived macrophages. IFN-β was expressed by mast cells in paws from naïve mice and during zymosan-induced inflammation. As described for macrophages the release of type I IFNs from mast cells depended on TLR internalization and endosome acidification. In conclusion, mast cells are able to produce several mediators including IFN-β, which are alone or in combination with each other able to regulate the phagocytotic activity of macrophages during resolution of inflammation.

scholarly journals Mast Cells Exert Anti-Inflammatory Effects in an IL10−/−Model of Spontaneous Colitis

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
E. M. Lennon ◽  
L. B. Borst ◽  
L. L. Edwards ◽  
A. J. Moeser
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Double Knockout ◽  
Significant Amelioration ◽  
Anti Inflammatory ◽  
Proinflammatory Role ◽  
Chemical Colitis

Mast cells are well established as divergent modulators of inflammation and immunosuppression, but their role in inflammatory bowel disease (IBD) remains to be fully defined. While previous studies have demonstrated a proinflammatory role for mast cells in acute models of chemical colitis, more recent investigations have shown that mast cell deficiency can exacerbate inflammation in spontaneous colitis models, thus suggesting a potential anti-inflammatory role of mast cells in IBD. Here, we tested the hypothesis that in chronic, spontaneous colitis, mast cells are protective. We compared colitis and intestinal barrier function in IL10−/−mice to mast cell deficient/IL10−/−(double knockout (DKO): KitWsh/Wsh × IL10−/−) mice. Compared with IL10−/−mice, DKO mice exhibited more severe colitis as assessed by increased colitis scores, mucosal hypertrophy, intestinal permeability, and colonic cytokine production. PCR array analyses demonstrated enhanced expression of numerous cytokine and chemokine genes and downregulation of anti-inflammatory genes (e.g.,Tgfb2,Bmp2,Bmp4,Bmp6, andBmp7) in the colonic mucosa of DKO mice. Systemic reconstitution of DKO mice with bone marrow-derived mast cells resulted in significant amelioration of IL10−/−-mediated colitis and intestinal barrier injury. Together, the results presented here demonstrate that mast cells exert anti-inflammatory properties in an established model of chronic, spontaneous IBD. Given the previously established proinflammatory role of mast cells in acute chemical colitis models, the present findings provide new insight into the divergent roles of mast cells in modulating inflammation during different stages of colitis. Further investigation of the mechanism of the anti-inflammatory role of the mast cells may elucidate novel therapies.

scholarly journals Role of mast cells in the generation of a T-helper type 2 dominated anti-helminthic immune response

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Nathan M. Ryan ◽  
Steve Oghumu
Keyword(s):  
Immune Response ◽  
Mast Cell ◽  
Mast Cells ◽  
Immune Cells ◽  
The Body ◽  
Peripheral Tissues ◽  
Adaptive Immune ◽  
Worm Expulsion ◽  
Deficient Mice

Abstract Mast cells are long-lived, innate immune cells of the myeloid lineage which are found in peripheral tissues located throughout the body, and positioned at the interface between the host and the environment. Mast cells are found in high concentrations during helminth infection. Using Kitw-sh mast cell deficient mice, a recently published study in Bioscience Reports by Gonzalez et al. (Biosci. Rep., 2018) focused on the role of mast cells in the immune response to infection by the helminth Hymenolepis diminuta. The authors showed that mast cells play a role in the modulation of Th2 immune response characterized by a unique IL-4, IL-5 and IL-13 cytokine profile, as well as subsequent robust worm expulsion during H. diminuta infection. Unlike WT mice which expelled H. diminuta at day 10, Kitw-sh deficient mice displayed delayed worm expulsion (day 14 post infection). Further, a possible role for mast cells in the basal expression of cytokines IL-25, IL-33 and thymic stromal lymphopoietin was described. Deletion of neutrophils in Kitw-sh deficient mice enhanced H. diminuta expulsion, which was accompanied by splenomegaly. However, interactions between mast cells and other innate and adaptive immune cells during helminth infections are yet to be fully clarified. We conclude that the elucidation of mechanisms underlying mast cell interactions with cells of the innate and adaptive immune system during infection by helminths can potentially uncover novel therapeutic applications against inflammatory, autoimmune and neoplastic diseases.

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.

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.

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.

The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E2

2018 ◽  
Vol 11 (556) ◽  
pp. eaao4354 ◽  
Author(s):  
Ivana Halova ◽  
Monika Bambouskova ◽  
Lubica Draberova ◽  
Viktor Bugajev ◽  
Petr Draber
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
And Function ◽  
Cell Chemotaxis

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non–T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2. Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2. Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

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