Nitric oxide pathway is induced by FcεRI and up‐regulated by stem cell factor in mouse mast cells

Bidri, Mohamed; Ktorza, Sandra; Vouldoukis, Ioannis; Goff, Liliane Le; Debré, Patrice; Guillosson, Jean‐Jacques; Arock, Michel

doi:10.1002/eji.1830271124

Cited by 42 publications

(35 citation statements)

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“…The source of NO in enteropathy has not been identified but a number of cells including epithelial cells, macrophages, and mast cells have been implicated (9,(43)(44)(45). Epithelial cells are the first point of host contact for invasive intestinal pathogens and may initiate mucosal inflammatory responses via production of proinflammatory cytokines and mediators including NO (8,43).…”

Section: Discussionmentioning

confidence: 99%

“…Mast cells have also been shown to induce intestinal pathology by a number of mechanisms including the release of mediators such as cytokines, histamine, and NO (32)(33)(34)49). There is also evidence that mast cells have the ability to synthesize and release NO derivatives through their own expression of iNOS induced by IgE immune complexes (44). Furthermore, iNOS has been shown to be crucial in allergic inflammatory processes by regulating the activation and degranulation of mast cells (50).…”

Section: Discussionmentioning

confidence: 99%

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Nitric Oxide Mediates Intestinal Pathology But Not Immune Expulsion DuringTrichinella spiralisInfection in Mice

Lawrence

Paterson

Wei

et al. 2000

The Journal of Immunology

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The relationship between intestinal pathology and immune expulsion of gastrointestinal (GI) nematodes remains controversial. Although immune expulsion of GI helminth parasites is usually associated with Th2 responses, the effector mechanisms directly responsible for parasite loss have not been identified. We have previously shown that while the intestinal pathology accompanying the expulsion of the GI parasite Trichinella spiralis may be dependent on IL-4 and mediated by TNF, parasite loss is independent of TNF. In contrast, intestinal pathology in other disease models has been attributed to Th1 cytokines, although it closely resembles that seen in helminth infections. Whereas production of inducible NO synthase (iNOS) in the gut is important for both homeostasis of the epithelial layer and in protection against pathogenic microorganisms, overproduction of NO has been implicated in the pathogenesis of a number of inflammatory conditions. We therefore investigated the role of NO in T. spiralis infection using iNOS-deficient mice. iNOS−/− and iNOS-/+ mice were infected with T. spiralis, and parasite expulsion and intestinal pathology were followed. Parasite expulsion proceeded similarly in both groups of animals, but significant intestinal pathology was only observed in the heterozygous mice. Thus it appears that, although the protective effects of Th2 responses in GI helminth infection do not require NO, this mediator contributes substantially to the associated enteropathy. NO may therefore be an important mediator of enteropathy in both Th1- and Th2-inducing conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Mediates Intestinal Pathology But Not Immune Expulsion DuringTrichinella spiralisInfection in Mice

Lawrence

Paterson

Wei

et al. 2000

The Journal of Immunology

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“…The present observation is basically in line with earlier findings of TNF-mediated enhanced production of NO in cultured peritoneal and intestinal mast cells (Bissonnette et al, 1991), however, NO production was at that time not attributable to a certain NOS isoform. There is inconsistent information about NOS isoenzyme expression in mast cells of different organs: positive bNOS immunoreactivity has been reported for human skin mast cells (Shimizu et al, 1997), whereas both mouse myometrial (Huang et al, 1995) and connective tissue mast cells (Bidri et al, 1997) showed iNOS expression after hormonal or antigen stimulation. Further studies should address the issue of whether the up-regulation of eNOS in response to LPS in mast cells as opposed to other cell types is a lung-specific finding or is representative for mast cells of other organ origin.…”

Section: Ermert Et Almentioning

confidence: 99%

Cell-Specific Nitric Oxide Synthase-Isoenzyme Expression and Regulation in Response to Endotoxin in Intact Rat Lungs

Ermert

Ruppert

Günther

et al. 2002

Laboratory Investigation

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SUMMARY:Nitric oxide (NO) produced by NO synthase (NOS) serves as a ubiquitous mediator molecule involved in many physiologic lung functions, including regulation of vascular and bronchial tone, immunocompetence, and neuronal signaling. On the other hand, excessive and inappropriate NO synthesis in inflammation and sepsis has been implicated in vascular abnormalities and cell injury. At least three different NOS isoforms (neuronal/brain [bNOS], inducible [iNOS], and endothelial [eNOS]) have been described, which are all expressed in normal lung tissue. We investigated the cell-specific expression of bNOS, iNOS, and eNOS in perfused control rat lungs and lungs undergoing stimulation with endotoxin in the presence and absence of plasma constituents. Lung immunohistochemistry and quantitative evaluation of staining intensity showed endotoxininduced increase in iNOS expression in particular in bronchial epithelial cells, cells of the bronchus-associated lymphoid tissue (BALT), alveolar macrophages, and vascular smooth muscle cells in a time-and dose-dependent fashion. In endothelial cells, which did not express iNOS at baseline, newly induced iNOS was found in response to endotoxin. In contrast, expression of eNOS was markedly suppressed under endotoxin challenge, particularly in bronchial epithelium, BALT, and alveolar macrophages but also in vascular smooth muscle cells and endothelial cells. eNOS expression in bronchial smooth muscle cells was not altered. In contrast to iNOS and eNOS, cellular expression of bNOS in epithelial cells, nerve fibers, BALT, and endothelial cells did not change in response to endotoxin. All changes in NOS regulation were found to be independent of plasma constituents. We conclude that endotoxin exerts a profound impact on the cell-specific NOS regulation in a large number of lung cell types. Prominent features include de novo synthesis or up-regulation of iNOS, in contrast to down-regulation of eNOS, which may well contribute to vascular abnormalities, inflammatory sequelae, and loss of physiologic functions in septic lung failure. (Lab Invest 2002, 82:425-441).

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“…Indeed, intracellular ROS generation has been reported for RPMC (17)(18)(19), a mouse mast cell line (20), RBL-2H3 cells, and mouse bone marrow-derived mast cells (21). To date, no studies have been performed with human mast cells.Reports from several groups claim that mast cells produce [22][23][24][25][26], although again, studies from our own laboratory (27-29) have provided contradictory evidence. Salvemini et al (22) reported the release of a NO-like activity from rat peritoneal mast cells, although their preparations contained up to 15% macrophages, a known source of NO.…”

mentioning

confidence: 91%

“…Salvemini et al (22) reported the release of a NO-like activity from rat peritoneal mast cells, although their preparations contained up to 15% macrophages, a known source of NO. Bidri et al (23) reported expression of the inducible form of NO synthase (NOS2) and nitrite production by mouse bone marrow-derived mast cells, whereas Gilchrist et al (24 -26) have demonstrated inducible or constitutive NOS expression, nitrite production, and intracellular NO-induced DAF fluorescence in activated RPMC and the human tumor-derived HMC-1 and LAD2 mast cell-like lines. In contrast, we found that interferon (IFN)-␥ stimulated or spontaneous NO production by rat or mouse peritoneal mast cells diminished as mast cells were progressively purified, such that even in preparations that contained 98 -99% mast cells, the NO production could be fully accounted for by the residual 1-2% non-mast cells (27,28).…”

mentioning

confidence: 99%

Rodent and Human Mast Cells Produce Functionally Significant Intracellular Reactive Oxygen Species but Not Nitric Oxide

Swindle

Metcalfe

Coleman

2004

Journal of Biological Chemistry

103

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In immunity, reactive oxygen species (ROS) and nitric oxide (NO) are important antimicrobial agents and regulators of cell signaling and activation pathways. However, the cellular sources of ROS and NO are much debated. Particularly, there is contention over whether mast cells, key secretory cells in allergy and immunity, can generate these chemical species, and if so, whether they are of functional significance. We therefore examined directly by flow cytometry the capacity of mast cells to generate intracellular ROS and NO using the respective cell-permeable fluorescent probes dichlorodihydrofluorescein and diaminofluorescein and evaluated the effects of inhibitors of ROS and NO synthesis on cell degranulation. For each of three mast cell types (rat peritoneal mast cells, mouse bone marrow-derived mast cells, and human blood-derived mast cells), degranulation stimulated by IgE/antigen was accompanied by production of intracellular ROS but not NO. Inhibition of ROS production led to reduced degranulation, indicating a facilitatory role for ROS, whereas NO synthase inhibitors were without effect. Likewise, bacterial lipopolysaccharide and interferon-␥ over a wide range of conditions failed to generate intracellular NO in mast cells, whereas these agents readily induced intracellular NO in macrophages. NO synthase protein, as assessed by Western blotting, was readily induced in macrophages but not mast cells. We conclude that rodent and human mast cells generate intracellular ROS but not NO and that intracellular ROS but not intracellular NO are functionally linked to mast cell degranulation.Mast cells are secretory cells central to specific and innate immunity, allergy, and inflammation (1-5). In specific IgEmediated responses, they are activated by antigen to release chemical mediators such as histamine, proteases, prostaglandins, and cytokines (1), whereas in innate responses to bacteria, they promote neutrophil phagocytosis (3, 4) and lymph node hyperplasia (5) via the production of tumor necrosis factor. In keeping with a role in innate defense, mast cells can directly phagocytose and kill bacteria (6). Essential to bacterial killing by "professional" phagocytic cells such as neutrophils and macrophages is the production of reactive oxygen species (ROS) 1 such as superoxide and hydrogen peroxide, nitrogen oxygen species such as nitric oxide (NO), and their combined product peroxynitrite (7-10). However, in mast cells, these pathways are less well characterized, and there is debate over whether mast cells generate biologically significant amounts of reactive oxygen and nitrogen species.Several studies (11-13) have reported that rat peritoneal tissue type mast cells (RPMC) or mast cells of the rat RBL-2H3 cell line (14, 15) release ROS into the extracellular milieu in response to a range of stimuli. These studies measured ROSinduced light emission by scintillation counting (11) or using luminol or the luciferin-related compound 2-methyl-6-(pmethoxyphenyl)-3-7-dihydroamidazo[1,2␣]pyrazine-3-one) (12)(13)(14)(15)...

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Nitric oxide pathway is induced by FcεRI and up‐regulated by stem cell factor in mouse mast cells

Cited by 42 publications

References 44 publications

Nitric Oxide Mediates Intestinal Pathology But Not Immune Expulsion DuringTrichinella spiralisInfection in Mice

Nitric Oxide Mediates Intestinal Pathology But Not Immune Expulsion DuringTrichinella spiralisInfection in Mice

Cell-Specific Nitric Oxide Synthase-Isoenzyme Expression and Regulation in Response to Endotoxin in Intact Rat Lungs

Rodent and Human Mast Cells Produce Functionally Significant Intracellular Reactive Oxygen Species but Not Nitric Oxide

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