Nitric Oxide Inhibits IgE-Dependent Cytokine Production and Fos and Jun Activation in Mast Cells

Davis, Beverley J.; Flanagan, Brian; Gilfillan, Alasdair M.; Metcalfe, Dean D.; Coleman, John W.

doi:10.4049/jimmunol.173.11.6914

Cited by 45 publications

(37 citation statements)

References 40 publications

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“…21 Considering the close proximity of mast cells to the vasculature, endothelial perturbation may contribute to mast cell activation in its vicinity. Nitric oxide (NO) inhibits FceRI-dependent cytokine release from mast cells, 38,39 but due to impairment of NO bioavailability in SCA, 40 mast cell activation may remain unregulated. Thus, the sickle microenvironment favors persistent endogenous mast cell activation, which may pose a major challenge to conventional anti-inflammatory therapies.…”

Section: Discussionmentioning

confidence: 99%

Mast cell activation contributes to sickle cell pathobiology and pain in mice

Vincent

Vang

Nguyen

et al. 2013

Blood

187

260

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Key Points• Inhibition of mast cells with cromolyn or imatinib results in reduced systemic inflammation and neurogenic inflammation in sickle mice.• Pharmacological inhibition or genetic depletion of mast cells in sickle mice ameliorates chronic and hypoxia/reoxygenationinduced pain.Sickle cell anemia (SCA) is an inherited disorder associated with severe lifelong pain and significant morbidity. The mechanisms of pain in SCA remain poorly understood.We show that mast cell activation/degranulation contributes to sickle pain pathophysiology by promoting neurogenic inflammation and nociceptor activation via the release of substance P in the skin and dorsal root ganglion. Mast cell inhibition with imatinib ameliorated cytokine release from skin biopsies and led to a correlative decrease in granulocyte-macrophage colony-stimulating factor and white blood cells in transgenic sickle mice. Targeting mast cells by genetic mutation or pharmacologic inhibition with imatinib ameliorates tonic hyperalgesia and prevents hypoxia/reoxygenation-induced hyperalgesia in sickle mice. Pretreatment with the mast cell stabilizer cromolyn sodium improved analgesia following low doses of morphine that were otherwise ineffective. Mast cell activation therefore underlies sickle pathophysiology leading to inflammation, vascular dysfunction, pain, and requirement for high doses of morphine. Pharmacological targeting of mast cells with imatinib may be a suitable approach to address pain and perhaps treat SCA. (Blood. 2013;122(11):1853-1862

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Section: Discussionmentioning

confidence: 99%

Mast cell activation contributes to sickle cell pathobiology and pain in mice

Vincent

Vang

Nguyen

et al. 2013

Blood

187

260

View full text Add to dashboard Cite

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“…Although the precise mechanisms of action are incompletely characterized, IgE has a wide spectrum of abilities to induce the production and secretion of inflammatory cytokines such as TNF-α and IL-6 [46]. Moreover, plasma IgE levels have been associated in some studies with the severity of allergic airway inflammation [47].…”

Section: Allergic Inflammation and Vitamin Ementioning

confidence: 99%

Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma model

Lim¹,

Vasu²,

Valacchi³

et al. 2008

Free Radical Research

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Allergic asthma is a complex immunologically mediated disease associated with increased oxidative stress and altered antioxidant defenses. It was hypothesized that α-tocopherol (α-T) decreases oxidative stress and therefore its absence may influence allergic inflammatory process, a pathobiology known to be accompanied by oxidative stress. Therefore, selected parameters of allergic asthma sensitization and inflammation were evaluated following ovalbumin sensitization and re-challenge of α-T transfer protein (TTP) knock-out mice (TTP -/-) that have greatly reduced lung α-T levels (e.g. < 5%) compared to their litter mate controls (TTP +/+ ). Results showed that severe α-T deficiency result in a blunted lung expression of IL-5 mRNA and IL-5 protein and plasma IgE levels compared with TTP +/+ mice following immune sensitization and rechallenge, although lung lavage eosinophil levels were comparable in both genomic strains. It is concluded that the initial stimulation of immune responses by the TTP -/-mice were generally blunted compared to the TTP +/+ mice, thus diminishing some aspects of subsequent allergic inflammatory processes.

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“…Single-cell suspensions from adult spleens were stained with different mixtures of fluorochrome-conjugated Abs (prepared at Stanford or obtained from BD Pharmingen) containing IgM (DS-1), IgD (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), B220 (RA3-6B2), CD5 (53-7.3), CD21 (7G6), CD23 (B3B4), CD16/32 (2.4G2), CD72 (K10.6), CD22 (Cy34.1), and CD19 (1D3). These stain sets also contained Cascade Blue-conjugated CD3⑀ (145-2C11), CD4 (GK1.5), CD8␣ (53-6.7), Gr-1 (RB6-8C5), and F4/80 Abs that are used to gate out irrelevant, non-B cells.…”

Section: High-dimension Facs Analysismentioning

confidence: 99%

CD72 Down-Modulates BCR-Induced Signal Transduction and Diminishes Survival in Primary Mature B Lymphocytes

Tung²,

Tarner

et al. 2006

The Journal of Immunology

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CD72, a 45-kDa type II transmembrane glycoprotein carrying an ITIM motif, is believed to be an inhibitory coreceptor of the BCR. Mature B cells lacking CD72 show enhanced Ca2+ mobilization and are hyperproliferative in response to BCR ligation. However, the signal transduction pathways downstream of BCR signaling that transmit the inhibitory effect of CD72 in mature B cells remain unknown. To address this question, we used hen egg lysozyme-specific BCR transgenic mice to elucidate the differential cell signaling between wild-type and CD72-deficient B cells in response to hen egg lysozyme Ag stimulation. Our results demonstrate that CD72 predominantly down-regulates the major signal transduction pathways downstream of the BCR, including NF-AT, NF-κB, ERK, JNK, p38-MAPK, and PI3K/Akt in mature B cells. CD72 ligation with anti-CD72 Ab (K10.6), which mimics the binding of CD100 (a natural ligand for CD72) to release the inhibitory function of CD72, augments cell proliferation, Ca2+ flux, IκBα activation, and ERK MAPK activity upon Ag stimulation in wild-type B cells. In addition, we show direct evidence that CD72 promotes cell cycle arrest and apoptosis after Ag stimulation in mature B cells. Taken together, our findings conclude that CD72 plays a dominant role as a negative regulator of BCR signaling in primary mature B lymphocytes.

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Nitric Oxide Inhibits IgE-Dependent Cytokine Production and Fos and Jun Activation in Mast Cells

Cited by 45 publications

References 40 publications

Mast cell activation contributes to sickle cell pathobiology and pain in mice

Mast cell activation contributes to sickle cell pathobiology and pain in mice

Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma model

CD72 Down-Modulates BCR-Induced Signal Transduction and Diminishes Survival in Primary Mature B Lymphocytes

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