Propofol Inhibits HIF-1α/NLRP3 Signaling Pathway and Mast Cell Activation to Ameliorate Airway Inflammation in Allergic Asthma

IntroductionAsthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on stabilizing mast cells and decreasing inflammatory mediator production. Safranal, one of the active compounds from Crocus sativus, shows many anti-inflammatory properties. In this study, we evaluated the effect of safranal in ovalbumin (OVA)-induced asthma model. Furthermore, we investigate the effectiveness of safranal on stabilizing mast cell and inhibiting the production of inflammatory mediators in passive systemic anaphylaxis (PSA) model.MethodsOVA-induced asthma and PSA model were used to evaluate the effect of safranal in vivo. Lung tissues were collected for H&E, TB, IHC, and PAS staining. ELISA were used to determine level of IgE and chemokines (IL-4, IL-5, TNF-α, and IFN-γ). RNA sequencing was used to uncovers genes that safranal regulate. Bone marrow-derived mast cells (BMMCs) were used to investigate the inhibitory effect and mechanism of safranal. Cytokine production (IL-6, TNF-α, and LTC4) and NF-κB and MAPKs signaling pathway were assessed.ResultsSafranal reduced the level of serum IgE, the number of mast cells in lung tissue were decreased and Th1/Th2 cytokine levels were normalized in OVA-induced asthma model. Furthermore, safranal inhibited BMMCs degranulation and inhibited the production of LTC4, IL-6, and TNF-α. Safranal inhibits NF-κB and MAPKs pathway protein phosphorylation and decreases NF-κB p65, AP-1 nuclear translocation. In the PSA model, safranal reduced the levels of histamine and LTC4 in serum.ConclusionsSafranal alleviates OVA-induced asthma, inhibits mast cell activation and PSA reaction. The possible mechanism occurs through the inhibition of the MAPKs and NF-κB pathways.

Abnormal Expression of Fcγ Receptors by Human Bone Marrow Mast Cells in Systemic Mastocitosis

The effect of bezuclastinib on the pathobiology of mastocytosis: Changes in BM mast cells, tryptase, and KIT p.D816V variant allele frequency from the pivotal summit trial

Ethanol extracts of Saururus chinensis suppress ovalbumin-sensitization airway inflammation

Changes in Activated Bone Marrow Macrophages and Mast Cells in Patients with Myelofibrosis Following Ruxolitinib Therapy

COVID-19 infection in patients with mast cell disorders including mastocytosis does not impact mast cell activation symptoms

Systemic mastocytosis (SM) is typically suspected in patients with cutaneous mastocytosis (CM). In recent years, the presence of clonal mast cells (MCs) in a subset of patients with systemic symptoms associated with MC activation in the absence of CM has been reported and termed monoclonal MC activation syndromes or clonal systemic MC activation syndromes. In these cases, bone marrow (BM) MC numbers are usually lower than in SM with CM, there are no detectable BM MC aggregates, and serum baseline tryptase is often <20 µg/l; thus, diagnosis of SM in these patients should be based on careful evaluation of other minor WHO criteria for SM in reference centers, where highly sensitive techniques for immunophenotypic analysis and investigation of KIT mutations on fluorescence-activated cell sorter-purified BM MCs are routinely performed. The prevalence of hymenoptera venom anaphylaxis (HVA) among SM patients is higher than among the normal population and it has been reported to be approximately 5%. In SM patients with IgE-mediated HVA, venom immunotherapy is safe and effective and it should be prescribed lifelong. Severe adverse reactions to hymenoptera stings or venom immunotherapy have been associated with increased serum baseline tryptase; however, presence of clonal MC has not been ruled out in most reports and thus both SM and clonal MC activation syndrome might be underdiagnosed in such patients. In fact, clonal BM MC appears to be a relevant risk factor for both HVA and severe reactions to venom immunotherapy, while the increase in serum baseline tryptase by itself should be considered as a powerful surrogate marker for anaphylaxis. The Spanish Network on Mastocytosis has developed a scoring system based on patient gender, the clinical symptoms observed during anaphylaxis and serum baseline tryptase to predict for the presence of both MC clonality and SM among individuals who suffer from anaphylaxis.

Immunophenotyping in systemic mastocytosis diagnosis: ‘CD25 positive' alone is more informative than the ‘CD25 and/or CD2' WHO criterion

Inhibition of nitric oxide synthesis augments pulmonary oedema in isolated perfused rabbit lung

TMT-based quantitative proteomics reveals suppression of SLC3A2 and ATP1A3 expression contributes to the inhibitory role of acupuncture on airway inflammation in an OVA-induced mouse asthma model

Efficacy of Avapritinib in Patients with Advanced Systemic Mastocytosis: Hematologic and Bone Marrow Responses from the Phase 2 Open-Label, Single-Arm, Pathfinder Study

The middle layer of Phyllostachys nigra var. henonis (PN), Bambusae Calulis in Taeniam, has been used for cough and sputum for a long time. Cough is one of the major symptoms of asthma. However, there were few of scientific investigation about PN. To investigate the positive effect of PN on asthma, we measured the production of IL-4 of bronchoalveolar lavage fluid (BalF), Immunoglobulin E (IgE) level of serum and immune cell infiltration at lung tissue by HE stain in ovalbumin (OVA) induced asthma murine model (Balb/C, female, 6 weeks). In asthma model, there was IL-4 of BalF decreased by PN, however, it was not significantly. The IgE induced by OVA in serum significantly decreased by PN (40 mg/kg). Furthermore, we observed the decrease of immune cell infiltration up-regulated by OVA in lung tissue. We focused on decrease of cell infiltration by PN. Intercellular adhesion molecule-1 (ICAM-1) and L-selectin regulate IgE production by controlling mast cell accumulation at sites of inflammation. And then we investigated the mRNA and protein levels of ICAM-1 and L-selectin in bone marrow mast cells (BMMC). BMMC were incubated with 10 ng/ml of TNF-alpha fnand IL-3 plus 1, 10 and 100 £gg/ml of PN for 4 hours. The mRNA and protein level were measeured by using RT-PCR and Fluorescence activated cell sorter (FACS). PN had down-regulated both mRNA and protein of ICAM-1, however, no difference at mRNA and protein of L-selectin in BMMC. Together all things, PN has anti allergy effects on asthma, based on down-regulation of ICAM-1. Acknowledgements: This study was supported by a grant from Seoul R&amp;BD Program, Republic of Korea.

Mast cell leukemia is characterized by proliferation and accumulation of immature mast cells in the bone marrow and other organs. The difficulties exist in the differential diagnosis of leukemic systemic mastocytosis and myelomastocytic leukemia. Although in both cases diagnostic criteria are reported, some questions about the terms remain to be open. This problem was discussed by the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) in 2011--2013. The diagnosis of myelomastocytic leukemia as myeloid tumor with a large number of mast cells was proposed as eligible in the absence of diagnostic criteria of mastocytosis. It was also recommended to divide leukemic systemic mastocytosis into acute and chronic forms based on the presence or absence of cutaneous manifestations. The primary form of the mast cell leukemia must be differentiated from the secondary, which usually develops in the set of aggressive systemic mastocytosis and mast cell sarcoma. The authors put emphasis on the inevitability of the prephase or leukemic systemic mastocytosis, which is often debut as aggressive systemic mastocytosis with rapid progression and the appearance of from 5 to 19% of mast cells in bone marrow smears. This condition is recommended to call the aggressive systemic mastocytosis in conversion to mast cells leukemia. The expansion of the current WHO classification by incorporating different variants of mast cell leukemia, will optimize the selection of patients for clinical trials.

Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed. Three extracts of A. aspera [aqueous (AaAq), hydroalcoholic (AaHA), ethanolic (AaEt)] were evaluated for their potency against C48/80-induced anaphylaxis in mice at 200mg/kg BW oral dose. The effective dose of the most potent extract was determined through its effect on C48/80-induced anaphylaxis, and was further analyzed through its effect on mast cell degranulation, histamine-induced bronchospasm and ovalbumin (OVA)-induced asthma in a murine model. Among the three extracts, AaAq was found to be most potent at 200mg/kg BW. AaAq 400 (400mg/kg BW) was found to be the most effective dose in terms of inhibition of mortality and histamine level. AaAq 400 prevented the peritoneal and mesenteric mast cells from undergoing morphological changes due to degranulation induced by C48/80. Further, AaAq 400 delayed pre-convulsive time in histamine-induced bronchospasm. In the OVA-induced asthma model, AaAq 400 inhibited the level of inflammatory cell count in blood, bronchoalveolar lavage fluid and peritoneal fluid of mice. The Th2 cytokines (IL-4, IL-5, IL-13), TGF-β and OVA-specific IgE were also reduced as evaluated by ELISA. Also, significant reduction in IL-5 (an eosinophilia indicator) transcript abundance and lung inflammatory score was observed. AaAq was safe up to 4000mg/kg BW. Thus AaAq 400 possesses significant antiallergic potential and acts via attenuation of C48/80-induced anaphylaxis and inhibition of mast cell degranulation. It reduces pre-convulsive dyspnea in histamine-induced bronchospasm and Th2 cytokines in asthmatic mice.

In this study the expression of 'classically' considered lymphoid-associated antigens (CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, and CD22) was explored both in peripheral blood (PB) and bone marrow (BM) mast cells (MC) in a case of systemic mast cell disease (SMCD) by means of using multiple stainings and a direct immunofluorescence technique. CD2 and CD22 were expressed in both PB and BM MC, all the remaining lymphoid-associated markers were negative. Our results suggest that the reactivity for both CD2 and CD22 in PB and BM MC would be aberrant.