scholarly journals Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation

2007 ◽  
Vol 204 (4) ◽  
pp. 907-920 ◽  
Author(s):  
Ai Masuda ◽  
Akira Nakamura ◽  
Tsutomu Maeda ◽  
Yuzuru Sakamoto ◽  
Toshiyuki Takai
Keyword(s):  
Mast Cells ◽  
Mhc Class I ◽  
Cell Activation ◽  
Human Leukocyte ◽  
Class I ◽  
Mast Cell Activation ◽  
Inhibitory Receptors ◽  
Immune Effector ◽  
Effector Cells ◽  
In Cis

Allergy is caused by immune effector cells, including mast cells and basophils. Cellular signaling that activates these effector cells is regulated by different inhibitory receptors on their surface. We show that human leukocyte immunoglobulin (Ig)-like receptor (LILR) B2 and its mouse orthologue, paired Ig-like receptor (PIR)–B, constitutively associate to major histocompatibility complex (MHC) class I on the same cell surface (in cis). The IgE-mediated effector responses were augmented in β2-microglobulin (β2m) and PIR-B–deficient mast cells. In addition, the increased cytokine production of β2m-deficient mast cells was not affected by the co-culture with MHC class I–positive mast cells, showing that less cis interaction between PIR-B and MHC class I on mast cells led to the increased cytokine release. Thus, the constitutive cis binding between LILRB2 or PIR-B and MHC class I has an essential role in regulating allergic responses.

scholarly journals Brain mast cells link the immune system to anxiety-like behavior

2008 ◽  
Vol 105 (46) ◽  
pp. 18053-18057 ◽  
Author(s):  
Katherine M. Nautiyal ◽  
Ana C. Ribeiro ◽  
Donald W. Pfaff ◽  
Rae Silver
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Neural Systems ◽  
Loss Of Function ◽  
Littermate Control ◽  
Cytokines And Chemokines ◽  
Function Models ◽  
The Brain

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

Association of Mast Cell Burden and TIM-3 Expression with Recalcitrant Chronic Rhinosinusitis with Nasal Polyps

2021 ◽  
pp. 000348942199503
Author(s):  
Michael A. Belsky ◽  
Erica Corredera ◽  
Hridesh Banerjee ◽  
John Moore ◽  
Li Wang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Cell Activation ◽  
Enzymatic Digestion ◽  
Sinus Surgery ◽  
Mast Cell Activation ◽  
Need For Treatment ◽  
Inflammatory State

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease. Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids. Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P = .02), stromal HR = 1.103 ( P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS. Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.

scholarly journals The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1759
Author(s):  
Yuhki Yanase ◽  
Shunsuke Takahagi ◽  
Koichiro Ozawa ◽  
Michihiro Hide
Keyword(s):  
Mast Cells ◽  
Cell Activation ◽  
Coagulation Factors ◽  
Chronic Spontaneous Urticaria ◽  
Mast Cell Activation ◽  
Coagulation Cascade ◽  
Edema Formation ◽  
Complement Components ◽  
Complement Factors

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by an almost daily recurrence of wheal and flare with itch for more than 6 weeks, in association with the release of stored inflammatory mediators, such as histamine, from skin mast cells and/or peripheral basophils. The involvement of the extrinsic coagulation cascade triggered by tissue factor (TF) and complement factors, such as C3a and C5a, has been implied in the pathogenesis of CSU. However, it has been unclear how the TF-triggered coagulation pathway and complement factors induce the activation of skin mast cells and peripheral basophils in patients with CSU. In this review, we focus on the role of vascular endothelial cells, leukocytes, extrinsic coagulation factors and complement components on TF-induced activation of skin mast cells and peripheral basophils followed by the edema formation clinically recognized as urticaria. These findings suggest that medications targeting activated coagulation factors and/or complement components may represent new and effective treatments for patients with severe and refractory CSU.

Abstract 1193: Mast Cell Activation Promotes Leukocyte Recruitment And Adhesion To The Atherosclerotic Plaque

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ilze Bot ◽  
Saskia C de Jager ◽  
Alma Zernecke ◽  
Christian Weber ◽  
Theo J van Berkel ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Cell Activation ◽  
Ex Vivo ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Mast Cell Activation ◽  
Labeled Leukocytes

Activated mast cells have been identified in the perivascular tissue of human coronary artery plaques. As mast cells have been described to release a whole array of chemokines including interleukin 8 (IL-8) and MIP1 α, we propose that activated mast cells play a pivotal role in leukocyte recruitment at advanced stages of atherosclerotic plaque development. Peritoneal mast cells of either C57Bl/6 or mast cell deficient Kit(W −sh /W −sh ) mice were activated by injection of compound 48/80 (1.2 mg/kg). Interestingly, mast cell activation led to a massive neutrophil influx into the peritoneal cavity at 3 hours after activation (controls: 1 ± 0.7*10 4 Gr1 + -neutrophils/ml up to 8 ± 0.2*10 4 Gr1 + neutrophils/ml at 3 hours after activation, *P<0.05), while neutrophil numbers in Kit(W −sh /W −sh ) mice were not affected by compound 48/80 administration. Moreover, increased levels of CXCR2 + Gr1 + neutrophils (t=0: 0.55 ± 0.07% versus t=3 hours: 1.00 ± 0.12%, *P<0.05) were observed after mast cell activation. Next, we investigated whether mast cell activation also translated in induced leukocyte adhesion to advanced atherosclerotic plaques. Adventitial mast cells of advanced collar aided carotid artery plaques were activated by local application of a dinitrophenyl-BSA (DNP) challenge in ApoE −/− mice. Three days later, the carotid artery segments carrying the plaques were isolated and perfused ex vivo with rhodamine labeled leukocytes, showing a dramatically increased number of adherent leukocytes after mast cell activation (49 ± 6 versus 19 ± 4 leukocytes/microscopic field for DNP versus control plaques, respectively, **P<0.001). Strikingly, antibody blockade of either the CXCR2 or VCAM-1 receptor VLA-4 on labeled leukocytes completely inhibited leukocyte adhesion to the atherosclerotic plaque (*P<0.05), while blockade of CCR1, -3 and -5 with Met-RANTES had no effect. In conclusion, our data suggest that chemokines such as IL-8 released from activated perivascular mast cells induce leukocyte recruitment and adhesion to the atherosclerotic plaque, aggravating the ongoing inflammatory response and thus effecting plaque destabilization. We propose that mast cell stabilization could be a new therapeutic approach in the prevention of acute coronary syndromes.

scholarly journals Mast cell activation is not required for induction of airway hyperresponsiveness by ozone in mice

1999 ◽  
Vol 86 (1) ◽  
pp. 202-210 ◽  
Author(s):  
N. Noviski ◽  
J. P. Brewer ◽  
W. A. Skornik ◽  
S. J. Galli ◽  
J. M. Drazen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Airway Hyperresponsiveness ◽  
Essential Role ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Polymorphonuclear Cell ◽  
Pulmonary Parenchyma

Exposure to ambient ozone (O3) is associated with increased exacerbations of asthma. We sought to determine whether mast cell degranulation is induced by in vivo exposure to O3in mice and whether mast cells play an essential role in the development of pulmonary pathophysiological alterations induced by O3. For this we exposed mast cell-deficient WBB6F1- kitW/ kitW-v( kitW/ kitW-v) mice and the congenic normal WBB6F1(+/+) mice to air or to 1 or 3 parts/million O3for 4 h and studied them at different intervals from 4 to 72 h later. We found evidence of O3-induced cutaneous, as well as bronchial, mast cell degranulation. Polymorphonuclear cell influx into the pulmonary parenchyma was observed after exposure to 1 part/milllion O3only in mice that possessed mast cells. Airway hyperresponsiveness to intravenous methacholine measured in vivo under pentobarbital anesthesia was observed in both kitW/ kitW-vand +/+ mice after exposure to O3. Thus, although mast cells are activated in vivo by O3and participate in O3-induced polymorphonuclear cell infiltration into the pulmonary parenchyma, they do not participate detectably in the development of O3-induced airway hyperresponsiveness in mice.

scholarly journals Granzyme D Is a Novel Murine Mast Cell Protease That Is Highly Induced by Multiple Pathways of Mast Cell Activation

2013 ◽  
Vol 81 (6) ◽  
pp. 2085-2094 ◽  
Author(s):  
Elin Rönnberg ◽  
Gabriela Calounova ◽  
Bengt Guss ◽  
Anders Lundequist ◽  
Gunnar Pejler
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Mast Cells ◽  
Serine Proteases ◽  
Cell Activation ◽  
Calcium Ionophore ◽  
Mast Cell Activation ◽  
Activated T Cells ◽  
Mast Cell Protease ◽  
Murine Mast Cell

ABSTRACTGranzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.

scholarly journals Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction

2021 ◽  
Author(s):  
Goutham Pattabiraman ◽  
Ashlee J Bell-Cohn ◽  
Stephen F. Murphy ◽  
Daniel J Mazur ◽  
Anthony J Schaeffer ◽  
...  
Keyword(s):  
Mast Cell ◽  
Smooth Muscle ◽  
Mast Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Critical Role ◽  
Smooth Muscle Contraction ◽  
Urinary Dysfunction ◽  
Mast Cell Activation ◽  
Prostate Inflammation

Intraurethral inoculation of mice with uropathogenic E. coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and in CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells using a combination of mast cell stabilizer (MCS), cromolyn sodium, and the histamine 1 receptor antagonist (H1RA), cetirizine di-hydrochloride, in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain (MLC)-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.

Sign in / Sign up

Export Citation Format

Share Document