Immunohistochemical Localization of Nitric Oxide Synthase in Normal Human Skin: Expression of Endothelial‐type and Inducible‐type Nitric Oxide Synthase in Keratinocytes

Shimizu, Yoshinori; Sakai, Masao; Umemura, Yoshiki; Ueda, Hiroshi

doi:10.1111/j.1346-8138.1997.tb02748.x

Cited by 104 publications

(64 citation statements)

References 64 publications

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“…It previously has been shown by immunohistochemistry that both human skin and nasal mucosal MCs also are positive for nNOS. 17,25 Thus, our nNOS results with ex vivo HSMCs are compatible with those in vivo studies, and there are significant differences in NOS expression in human MC populations contributing further to MC heterogeneity.With the lack of constitutive iNOS expression, human MCs appear to rely on constitutive (cNOS) in their quiescent state. This pattern is reiterated in other human immune cells, with neutrophils and eosinophils also being identified as cNOS expressors, employing eNOS and nNOS isoforms.…”

supporting

confidence: 77%

Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production

Gilchrist

McCauley

Befus

2004

Blood

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Nitric oxide (NO) is a potent radical produced by nitric oxide synthase (NOS) and has pleiotrophic activities in health and disease. As mast cells (MCs) play a central role in both homeostasis and pathology, we investigated NOS expression and NO production in human MC populations. Endothelial NOS (eNOS) was ubiquitously expressed in both human MC lines and skin-derived MCs, while neuronal NOS (nNOS) was variably expressed in the MC populations studied. The inducible (iNOS) isoform was not detected in human MCs.Both growth factor-independent (HMC-1) and -dependent (LAD 2) MC lines showed predominant nuclear eNOS protein localization, with weaker cytoplasmic expression. nNOS showed exclusive cytoplasmic localization in HMC-1. Activation with Ca 2؉ ionophore (A23187) or IgE-anti-IgE induced eNOS phosphorylation and translocation to the nucleus and nuclear and cytoplasmic NO formation. eNOS colocalizes with the leukotriene (LT)-initiating enzyme 5-lipoxygenase (5-LO) in the MC nucleus. The NO donor, S-nitrosoglutathione (SNOG), inhibited, whereas the NOS inhibitor, N G -nitro-L-arginine methyl ester (L-NAME), potentiated LT release in a dose-dependent manner. Thus, human MC lines produce NO in both cytoplasmic and nuclear compartments, and endogenously produced NO can regulate LT production by MCs. IntroductionMast cells (MCs) are tissue-resident effector cells that arise from bone marrow precursors. 1 They produce and secrete numerous bioactive agents and have been implicated in diverse homeostatic functions such as angiogenesis, wound healing, and tissue remodeling. 2 Due to their plethora of mediators and strategic localization, MCs also play central roles in various disease states, including multiple sclerosis and T-helper type 2 (T H 2)-driven inflammatory conditions such as asthma. 3,4 Nitric oxide (NO) is a potent radical with diverse roles in regulating cellular activation. 5 NO is derived from L-arginine by the nitric oxide synthase (NOS) family of enzymes. The Ca 2ϩ -dependent members include endothelial (eNOS) and neuronal (nNOS), characterized by constitutive expression and low NO production. Inducible NOS (iNOS) is up-regulated by a variety of inflammatory mediators and functions independently of cellular Ca 2ϩ levels and releases large amounts of NO. 6 Numerous investigators have shown that rodent MCs are regulated by endogenous NO from both constitutive and inducible sources. 7,8 However, little is known about the production of NO by human MCs or the potential involvement of NO as modulator of human MC function.The aim of this study was to investigate the expression of NOS and production of NO in human MCs. Furthermore, we studied the regulation of NOS and the resulting functional effects on the release of leukotrienes. Our results indicate that NO may be a novel modulator that determines the functional phenotype of human MCs. Materials and methods ReagentsThe NOS inhibitor N G -nitro-L-arginine methyl ester (L-NAME), inactivate enantiomer N G -nitro-D-arginine methyl ester (D-NAME), and NO donor S-n...

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supporting

confidence: 77%

Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production

Gilchrist

McCauley

Befus

2004

Blood

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“…We also detected eNOS gene transcriptional expression through RT-PCR analysis, suggesting that eNOS is synthesized by umbilical cord cells. In agreement with our data, eNOS expression, typical of endothelia, has also been reported in other types of tissues and cells, such as many epithelium, fibroblasts, cardiomyocytes, osteocytes and glial cells [32][33][34][35].…”

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confidence: 92%

Human umbilical cord expresses several vasoactive peptides involved in the local regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin, ANP, eNOS and iNOS

Mauro¹,

Buscemi²,

Provenzano³

et al. 2011

Folia Histochem Cytobiol.

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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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Immunohistochemical Localization of Nitric Oxide Synthase in Normal Human Skin: Expression of Endothelial‐type and Inducible‐type Nitric Oxide Synthase in Keratinocytes

Cited by 104 publications

References 64 publications

Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production

Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production

Human umbilical cord expresses several vasoactive peptides involved in the local regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin, ANP, eNOS and iNOS

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

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