scholarly journals Role of platelet activating factor (PAF) on leukocyte-independent plasma extravasation and mast cell activation during endotoxemia

Critical Care ◽  
10.1186/cc776 ◽  
2000 ◽  
Vol 4 (Suppl 1) ◽  
pp. P56
Author(s):  
A Walther ◽  
N Yilmaz ◽  
W Schmidt ◽  
A Secchi ◽  
MM Gebhard ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Platelet Activating Factor ◽  
Mast Cell Activation ◽  
Plasma Extravasation

Role of Platelet-Activating Factor in Leukocyte-Independent Plasma Extravasation and Mast Cell Activation during Endotoxemia

2000 ◽  
Vol 93 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Andreas Walther ◽  
Nevin Yilmaz ◽  
Werner Schmidt ◽  
Alfons Bach ◽  
Martha Maria Gebhard ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Platelet Activating Factor ◽  
Mast Cell Activation ◽  
Plasma Extravasation

Nitric oxide positively regulates Ag (I)-induced Ca2+ influx and mast cell activation: role of a nitric oxide synthase-independent pathway

2009 ◽  
Vol 86 (6) ◽  
pp. 1365-1375 ◽  
Author(s):  
Toshio Inoue ◽  
Yoshihiro Suzuki ◽  
Tetsuro Yoshimaru ◽  
Chisei Ra
Keyword(s):  
Nitric Oxide ◽  
Mast Cell ◽  
Nitric Oxide Synthase ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Oxide Synthase

Critical role of IgE-dependent mast cell activation in a murine model of allergic conjunctivitis

2009 ◽  
Vol 124 (4) ◽  
pp. 827-833.e2 ◽  
Author(s):  
Ken Fukuda ◽  
Masaharu Ohbayashi ◽  
Kei Morohoshi ◽  
Lane Zhang ◽  
Fu-Tong Liu ◽  
...  
Keyword(s):  
Mast Cell ◽  
Murine Model ◽  
Allergic Conjunctivitis ◽  
Cell Activation ◽  
Critical Role ◽  
Mast Cell Activation

Mast Cell Activation and the Role of Eicosanoids

2009 ◽  
pp. 91-99
Author(s):  
E. Nigel Wardle
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Mast Cell Activation

scholarly journals Differential use of BTK and PLC in FcεRI- and KIT-mediated mast cell activation: A marginal role of BTK upon KIT activation

2020 ◽  
Vol 1867 (4) ◽  
pp. 118622
Author(s):  
Anne Simonowski ◽  
Thomas Wilhelm ◽  
Pardes Habib ◽  
Carolin N. Zorn ◽  
Michael Huber
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Mast Cell Activation

Mast Cell Activation Contributes to Neurogenic Inflammation and Pain in Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 374-374
Author(s):  
Lucile Vincent ◽  
Julia Nguyen ◽  
Derek Vang ◽  
Oludare B Taiwo ◽  
Kathryn Luk ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Neurogenic Inflammation ◽  
Control Mouse ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Plasma Extravasation ◽  
Cell Disease ◽  
Gm Csf ◽  
Skin Biopsies

Abstract Abstract 374 Sickle cell disease (SCD) is associated with inflammation, endothelial dysfunction and pain. We observed increased immunoreactivity (ir) of pro-inflammatory and vasoactive neuropeptides, substance P (SP) and calcitonin-gene related peptide (CGRP) accompanied by decreased mu opioid receptor (MOR)-ir in the skin of sickle as compared to control mice (Kohli et al., Blood 2010). SP activates mast cells (MC), which are tissue resident leukocytes, leading to the release of inflammatory cytokines, tryptase and neuropeptides. SP also stimulates vascular permeability resulting in plasma extravasation and neurogenic inflammation. We hypothesized that pain in SCD is associated with a persistent feed-forward cycle of mast cell degranulation and neurogenic inflammation characterized by increased release of SP and CGRP from activated nociceptors in the skin leading to neuroinflammation, plasma extravasation and pain. We examined this hypothesis using sickle (HbSS-BERK) and control (HbAA-BERK) mice expressing sickle and normal human hemoglobin, respectively; and MOR-knockout (MOR-KO) mice with their wild type 129S6 controls. We developed an ex-vivo system to analyze the release of inflammatory cytokines, mast cell degranulation markers (tryptase and beta-hexosaminidase) and neuropeptides in skin biopsies. Neurogenic inflammation was studied in vivo using the Miles' assay. Evans blue was injected into the tail vein and its extravasation in skin evoked by stimulation with SP and capsaicin was quantified. Skin biopsies from sickle mice exhibited constitutively enhanced release of several cytokines (IL6, MCP-1, TNFalpha, MIP-1alpha, GM-CSF, RANTES, etc), tryptase and the neuropeptides SP, and CGRP as compared to control mouse skin (p<0.05 for each). Increased RANTES and GM-CSF are suggestive of mast cell recruitment. Mast cell tryptase-ir was increased 2-fold while MOR-ir (but not delta- or kappa-OR-ir), was reduced by ∼50% in the skin of sickle as compared to control mice, suggestive of enhanced MC degranulation in sickle. In MC cultures prepared from sickle skin increased c-kit/CD117-, FCeR- and tryptase-ir were observed as compared to control mouse MCs. The plasma of sickle exhibited a ∼60–80% increase in MC degranulation markers, tryptase and beta-hexosaminidase, acute phase protein, serum amyloid protein, and neuropeptides, SP and CGRP, as compared to control mice (p<0.01 for each). These correlative molecular changes in the plasma and skin were accompanied by increased SP- and capsaicin-induced Evans blue dye leakage in the skin of sickle mice suggestive of neurogenic inflammation as compared to control (p<0.001 for each). MOR-KO mice also exhibited increased SP- and CGRP-ir in the skin and neurogenic inflammation, indicative of a contribution by MOR to the neuroinflamamtory process. In sickle mice treated with the mast cell stabilizer cromolyn sodium (CS), or the c-kit inhibitor, Imatinib, for 5 days, the inflammatory cytokine and neuropeptide release from the skin and the neurogenic inflammation were ameliorated as compared to vehicle (p<0.01). Additionally, morphine at a dose of 10 mg/Kg was ineffective in treating tonic cutaneous and thermal hyperalgesia, but effectively reduced hyperalgesia in CS and Imatinib treated sickle mice. Thus, MC degranulation contributes to neurogenic inflammation and pain in sickle mice. Imatinib treatment by itself reduced tonic hyperalgesia and significantly decreased GM-CSF release from the skin (p<0.05) correlative to the reduced white blood cell (WBC) count in sickle mice vs vehicle. In addition to inhibiting MC activity, Imatinib may be inhibiting protein tyrosine kinases involved in cytokine processing, vascular function and nociception. Together, our observations demonstrate that MCs contribute to a vicious cycle of pain and neurogenic inflammation mediated by increased neuropeptides in SCD. It is likely that mast cell inhibitors such as Imatinib may have a therapeutic effect on pain, inflammation and vascular dysfunction in SCD by reducing mast cell activation and neurogenic inflammation. Since, Imatinib decreased GM-CSF levels and WBC, it may even increase HbF levels, which are negatively regulated by GM-CSF in SCD. We therefore speculate that therapies targeting mast cells may potentiate therapeutic outcomes of analgesics, anti-inflammatory agents and Hydroxyurea® in SCD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis

2016 ◽  
Vol 10 ◽  
pp. 16-23 ◽  
Author(s):  
Jianping Li ◽  
Shaiban Jubair ◽  
Scott P. Levick ◽  
Joseph S. Janicki
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Mast Cell Activation

A new chemical tool (C0036E08) supports the role of adenosine A2B receptors in mediating human mast cell activation

2008 ◽  
Vol 76 (7) ◽  
pp. 912-921 ◽  
Author(s):  
Montserrat Buceta ◽  
Eduardo Domínguez ◽  
Marián Castro ◽  
José Brea ◽  
David Álvarez ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Human Mast Cell ◽  
Adenosine A2b

scholarly journals Dnmt3arestrains mast cell inflammatory responses

2017 ◽  
Vol 114 (8) ◽  
pp. E1490-E1499 ◽  
Author(s):  
Cristina Leoni ◽  
Sara Montagner ◽  
Andrea Rinaldi ◽  
Francesco Bertoni ◽  
Sara Polletti ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mast Cell ◽  
Cell Biology ◽  
Dna Methyltransferase ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Mast Cell Activation ◽  
Cell Responses

DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations inDNMT3Acorrelate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using mast cells lackingDnmt3a, we found that this enzyme is involved in restraining mast cell responses to acute and chronic stimuli, both in vitro and in vivo. The exacerbated mast cell responses observed in the absence ofDnmt3awere recapitulated or enhanced by treatment with the demethylating agent 5-aza-2′-deoxycytidine as well as by down-modulation ofDnmt1expression, further supporting the role of DNA methylation in regulating mast cell activation. Mechanistically, these effects were in part mediated by the dysregulated expression of the scaffold protein IQGAP2, which is characterized by the ability to regulate a wide variety of biological processes. Altogether, our data demonstrate that DNMT3A and DNA methylation are key modulators of mast cell responsiveness to acute and chronic stimulation.

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