IgE and IgA produced by OX40-OX40L or CD40-CD40L interaction in B cells-mast cells re-activate FcεRI or FcαRI on mast cells in mouse allergic asthma

Hong, G.U.,Lim, J.Y.,Kim, N.G.,Shin, J.H.,Ro, J.Y. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.754 No.-

<P>Mast cells are major effector cells of allergic diseases related to NE. This study was undertaken to determine whether IgE or IgA, produced by CD40-CD40L or OX40-OX40L interactions between B cells and mast cells, re-activate Fc epsilon RI or Rat on mast cell surface. C57BL mice were sensitized and subjected to OVA challenge to induce asthma. Bone marrow-derived mast cells (BMMCs) and primary B cells were co-cultured. Mast cell recruitment into airways was stained by May-Grunwald Giemsa, the expression of markers or signaling molecules were determined by immunohistochemistry or Western blotting, and co-localization of B cells and mast cells by immunofluorescence. Anti-CD40 plus anti-OX40L Abs synergistically reduced IgE and IgA production, and mediators (histamine, LTs and cytokines) released in mast cells, and additively reduced other responses, such as, numbers of mast cells, the expression of markers (tryptase, mMCP5, B220 and CD19), surface molecules (CD40, CD40L, OX40 and OX40L), Fc epsilon RI or Fc alpha RI and the co-localization of BMMCs and B cells, and IgE- or IgA-producing cells, as compared with individual blocking Ab treatment which reducedresponses in BAL cells or lung tissues of OVA-challenged mice or in co-culture of B and mast cells. The data suggest that IgE and IgA, produced by OX40-OX40L or CD40-CD40L interaction between B cells and mast cells, may re-activate receptors of FC epsilon RI and Fc alpha RI on mast cell surfaces, followed by more mediator release, and furthermore, that treatment with anti-CD40 plus anti-OX40L Abs offers a potential treatment for allergic asthma. (C) 2015 Elsevier B.V. All rights reserved.</P>

Regional Differences in Chronic Stress-induced Alterations in Mast Cell and Protease-activated Receptor-2-positive Cell Numbers in the Colon of Ws/Ws Rats

( Yong Sung Kim ),( Moon Young Lee ),( Han Seung Ryu ),( Eul Sig Choi ),( Jung Taek Oh ),( Ki Jung Yun ),( Suck Chei Choi ) 대한소화기기능성질환·운동학회 2014 Journal of Neurogastroenterology and Motility (JNM Vol.20 No.1

Background/Aims There have been no reports on the effect of chronic psychological stress on colonic immune cells or the regional differences. We aimed to investigate the effect of chronic psychological stress on the number of mast cells and protease-activated receptor (PAR)-2-positive cells in the rat colonic mucosa. Methods Six-week-old and 14-week-old Ws/Ws rats, which lack mast cells after 10 weeks, were used as control and mast cell-deficient groups, respectively. The rats were divided into stress and sham-treated groups. Rats in the stressed group were exposed to water avoidance stress (WAS, 1 hour/day) for 13 days. Fecal pellet output and the number of mast cells and PAR-2-positive cells in colonic mucosa were compared between the WAS and sham groups. Results In 6-week-old rats, the WAS group showed a significantly higher number of mast cells compared to the sham group. In 14-week-old rats, mast cells were nearly absent in the colonic mucosa. WAS significantly increased PAR-2-positive cells in 14-week-old rats, but not in 6-week-old rats. Indirect estimation of PAR-2-positive mast cells in 6-week-old rats suggested that the majority of increased mast cells following WAS did not express PAR-2. WAS increased mast cells and PAR-2-positive cells mainly in the proximal colon. Fecal pellet output was continuously higher in the WAS group than in the sham group, and the difference was significant for both 6-week-old and 14-week-old rats. Conclusions Chronic psychological stress increased the number of mast cells and PAR-2-positive cells in rat colonic mucosa, and these in- creases were more prominent in the proximal colon. (J Neurogastroenterol Motil 2014;20:54-63)

Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-${\alpha}$

Chai, Ok-Hee,Han, Eui-Hyeog,Lee, Hern-Ku,Song, Chang-Ho Korean Society for Biochemistry and Molecular Bion 2011 Experimental and molecular medicine Vol.43 No.1

Mast cells are well recognized as key cells in allergic reactions, such as asthma and allergic airway diseases. However, the effects of mast cells and TNF-${\alpha}$ on T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood. Therefore, an aim of this study was to investigate the role of mast cells on Th2 cytokine-dependent airway hyperresponsiveness and inflammation. We used genetically mast cell-deficient WBB6F1/J-$Kit^W$/$Kit^{W-v}$ ($W/W^v$), congenic normal WBB6F1/J-$Kit^+$/$Kit^+$ (+/+), and mast cell-reconstituted $W/W^v$ mouse models of allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal injection of TNF-${\alpha}$ directly induce the expression of ICAM-1 and VCAM-1 in $W/W^v$ mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness, and increased levels of TNF-${\alpha}$, intercellular adhesion molecule (ICAM)-1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in $W/W^v$ mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted $W/W^v$ mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-${\alpha}$ resulted in increased ICAM-1 and VCAM-1 protein levels in $W/W^v$ mice. These results suggest that mast cells play a key role in a Th2 cytokine-dependent asthma model through production of adhesion molecules, including ICAM-1 and VCAM-1, by liberation of TNF-${\alpha}$.

Oleanolic Acid Acetate Inhibits Mast Cell Activation in Ovalbumin-Induced Allergic Airway Inflammation

Kim Yeon-Yong,Lee Soyoung,Kim Min-Jong,Rho Mun-Chual,장용현,Kim Sang-Hyun 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.2

Purpose: Asthma is a complex, heterogeneous chronic inflammatory airway disease with multiple phenotypes. There has been a great progress in managing asthma, but there are still unmet needs for developing uncontrolled asthma treatments. The present study aimed to determine the effectiveness of oleanolic acid acetate (OAA) from Vigna angularis against allergic airway inflammation and the underlying mechanism of action with a focus on mast cells. Methods: To investigate the effect of OAA in allergic airway inflammation, we used the ovalbumin (OVA)-sensitized and challenged mice. To examine allergic airway inflammation associated with immune responses of mast cell activation in vitro, various types of mast cells were used. Systemic and cutaneous anaphylaxis models were used for mast cell-mediated hyper-responsiveness in vivo. Results: OAA reduced OVA-induced airway inflammatory responses such as bronchospasm, increase of immune cell infiltration and serum immunoglobulin E and G1 levels. Especially, OAA decreased the mast cell infiltration, and β-hexosaminidase release as a mast cell activation marker in the bronchoalveolar lavage fluid. OAA inhibited mast cell degranulation in mast cell line (RBL-2H3) and primary cells (rat peritoneal mast cell and mouse bone marrow-derived mast cell). Mechanistically, OAA suppressed intracellular signaling pathways including the phosphorylation of phospholipase Cγ and nuclear factor-κB, resulting from the suppression of intracellular calcium influx and pro-inflammatory cytokine expression. Further, oral administration of OAA attenuated mast cell-mediated systemic and cutaneous anaphylaxis. Conclusions: Our study showed that OAA can inhibit mast cell-mediated allergic reaction. Consequently, the application of OAA to mast cells for the allergic airway inflammation facilitate a new direction of treating allergic asthma.

사염화탄소 유도 간섬유증 발생에 었어서 비만세포와 근섬유모세포의 상호 관련성

제갈승주 ( Seung Joo Jakal ) 대한임상검사과학회 2001 대한임상검사과학회지(KJCLS) Vol.33 No.2

Hepatic fibrosis is known to be developed by producing the extracellular matrices from myofibroblasts(a-SMA postive cells) that are transformed from hepatic satellite cells. The development of the fibrotic process is thought to be mediate by various fibrogenic mediators. Recent1y, several studies have suggested that mast cells participate in the development of the hepatic fibrosis in human liver diseases and in rodent models. But The close relation between mast cells and myofibroblasts in the development of hepatic fibrosis remains still llllclear. In this study We have investigated the change of collagen content, the disπibution and density of mast cells and myofibrobalsts during 2, 4, 6-week after carbon tetrachloride treatment in rat. Twenty male Wistar rats were divided into four groupsincluding control. Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride(CC14) in rats. πle degree of fibrosis was evaluated by measuring the hydroxyproline content(ugjg tissue) of the liver as an index of the collagen content and by using a numerical scoring system for grading hepatic fibrosis in the liver sections stained with Masson trichrome and Gomori reticulum, respectively. The density of mast cells (number/mmj was determined by cOllllting mast cells using a computerized image analyser system in liver sections stained with toluidine blue and alcian blue-safranin O, respectively. Also, πle morphological relation between mast cells and myofibloblasts was examined by elecπon microscopy. πle c이lagen content was significant1y increased at 4 to 6week after CC4 treatment compared with control rats. These results showed significant correlations (Spe따man’ s,r=O.76, p<0.001) with those of a numerical scoring system. In control rats, mast cells were found principally in portal areas, and their average density was 4.76 i= 2.23/ MM2 in liver sections stained with alcian blue-safranin O. Whereas in CC4-treated rats mast cells were diffusely distributed in fibrous septa and fibrous capsule on liver surface and were significantly increased at 2(8.86 i= 1.94/mnf), 4(12.26 i= 3.59/mm2 to 6week(28.09 i= 12.74/ mm2)after CC4 treatment compared with control rats. In cαltrol rats, myofibroblasts were not found in portal areas and observed only Q-SMA positive staining on vessel walls in portal areas. In CC4-treated rats, myofibroblasts were occasionally found at 2week after CC4 treatment in portal areas, fibrous septa and liver parencyma, but were statistically not significant compared with control rats. Myofibrobasts were significantly increased at 4 to 6week after CC4 treatment. U1trastructurally, mast cel1s were observed in close contact with myofibroblasts in fibrous septa and showed the various stages of degranulation. πlese results suggested that mast cell may play role in deve10pment of hepatic fibrosis, probably because of the production of extracellular maπix components by myofibroblasts which activate by some mediators released from mast cells.

Reassessing the Roles of T Lymphocytes and Mast Cells in the Pathogenesis of Allergic Rhinitis

Pawankar, Ruby Korean Rhinologic Society 1999 Journal of rhinology Vol.6 No.1

꿩 전위의 비만세포에 관한 형태학적 연구

이영훈,Lee Y. H. 한국가금학회 2005 韓國家禽學會誌 Vol.32 No.2

Mast cells have been studied extensively in various animals including rats and mice, whereas little is known the morphological data about pheasant mast cells. Here, morphological features of Korean pheasant mast cells are described in this study using light and electron microscopes. For light microscopy, mast cells had many metachromatic granules stained with toluidine blue in the cytoplasm. The fixation with $10\%$ neutral buffered formalin blocked staining of most mast cells but a modified Karnovsky solution proved to be a good fixative. In Korean pheasants, toluidine blue stained more mast cells than did alcian blue. For electron microscopy, the mast cells of the Korean pheasant were round, oval, spindle-like and irregular form and occasionally had a few short cytoplasmic processes. These cells had membrane-bounded granules and poorly developed organells. Some granules in the cytoplasm of the mast cells had bilayer membrane. Most granules were round shape and the membrane of several granules was concave or convex. The granules were composed of three parts, homogenous, particulate and reticular pattern. 꿩 비만세포는 원형, 난원형, 방추형 또는 부정형이었고 세포질돌기를 가지고 있었다. 꿩 비만세포는 Karnovsky 용액으로 고정했을 때 가장 좋은 염색성을 얻었고, Toluidine blue로 염색을 했을 때 비만세포의 과립은 이염색성(meta-chromatic)을 나타내었다. 비만세포의 세포질에는 막으로 둘러싸인 과립과 발달이 미약한 세포소기관으로 채워져 있었다. 비만세포의 과립은 원형과 난원형이었고 일부 과립은 막이 함몰된 오목한 모양과 밖으로 돌출된 볼록한 모양이었다. 과립 속의 구조는 동질성, 입자형 또는 망상형이었다.

Reaction of Mast Cells and Goblet Cells in the Small Intestine of C57BL/6 and C3H/HeN Mice Infected with Echinostoma hortense

Park Kyeong-Yeol,Lee Kyu-Jae,Kim In-Sik,Yang Eun-Ju,Lim Su-jung,Lim Byung-Hyuk,Ryang Yong-Suk The Korean Society for Biomedical Laboratory Scien 2005 Journal of biomedical laboratory sciences Vol.11 No.3

Mast cells and goblet cells have been known to protect the host against parasites. In this study, we examined the response of the mast cells and goblet cells over a period of 6 weeks in the duodenum, jejunum and ileum of C3H/HeN and C57BL/6 mice infected with Echinostoma hortense (E. hortense). In addition, we investigated whether the worm recovery rate of uninfected mice (the control group) or E. hortense-infected mice (the experimental group) was associated with the number of mast cells and goblet cells. The worm recovery rate was higher in the C3H/HeN mice than in the C57BL/6 mice. The number of goblet cells significantly increased in the experimental group of the C3H/HeN and C57BL/6 mice compared with the control group of both strains (P<0.005). Worm recovery peaked 3 weeks after the infection of the C57BL/6 mice and at 2 weeks after the infection of the C3H/HeN mice, and it was higher in the duodenum than in the jejunum and ileum. However, the infected site in the intestine had no relation with worm expulsion. In the C3H/HeN and C57BL/6 mice, the number of goblet cells in the experimental group was significantly higher than that in the control group (P<0.005). The number reached a peak 2 weeks after the infection and it even increased in duodenum, jejunum and ileum. The increased number of goblet cells was retained 6 weeks after infection. The number of goblet cells was higher in the C3H/HeN mice than in the C57BL/6 mice (P<0.01). These results indicate that goblet cells are related with the worm expulsion. Furthermore, immunohistostaining of the antral intestinal walls for lectin showed the significant increase of the number of goblet cells in the experimental group (P<0.001). The high infection rate in the duodenum was found during the early infection. An increased infection rate in the jejunum and ileum was found 3 weeks after infection and the infection rate was higher in the C3H/HeN mice than in the C57BL/6 mice. Taken together, the present study indicates that goblet cells, rather than mast cells, may play critical roles in parasite expulsion.

Tumor associated mast cells: biological roles and therapeutic applications

Shikha Saxena,Anil Singh,Priyanka Singh 대한해부학회 2020 Anatomy & Cell Biology Vol.53 No.3

Mast cells (MCs) are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of MCs significantly modulates many aspects of physiological and pathological conditions in various settings. Recent data have expanded the concept that inflammation is a critical component for tumor progression. Interestingly, three of the most aggressive human cancers, malignant melanoma, breast carcinoma and colorectal adenocarcinoma, are commonly associated with a marked host response comprising of various inflammatory cells, but especially MCs around the tumor periphery. A systematic review of the literature was performed based on the English titles listed in the PubMed, EBSCO, Cochrane, Science Direct, ISI web Science, and SciELO databases using the keywords. Abstracts and full-text articles were assessed. This review summarizes the current understanding of the role of MCs in tumor progression.

Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-α

Ok Hee Chai,Chang Ho Song,Eui-Hyeog Han,Hern-Ku Lee 생화학분자생물학회 2011 Experimental and molecular medicine Vol.43 No.1

Mast cells are well recognized as key cells in allergic reactions, such as asthma and allergic airway diseases. However, the effects of mast cells and TNF-αon T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood. Therefore, an aim of this study was to investigate the role of mast cells on Th2cytokine-dependent airway hyperresponsiveness and inflammation. We used genetically mast cell-deficient WBB6F1/J-KitW/KitW-v (W/Wv), congenic normal WBB6F1/J-Kit+/Kit+ (+/+), and mast cell-reconstituted W/Wv mouse models of allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal injection of TNF-α directly induce the expression of ICAM-1 and VCAM-1 in W/Wv mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness,and increased levels of TNF-α, intercellular adhesion molecule (ICAM)-1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-α resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice. These results suggest that mast cells play a key role in a Th2cytokine-dependent asthma model through production of adhesion molecules, including ICAM-1 and VCAM-1, by liberation of TNF-α.