Bacterial infection induces nitric oxide synthase in human neutrophils.

Wheeler, Marcia A.; Smith, Shannon D.; García‐Cardeña, Guillermo; Nathan, Carl; Weiß, Robert M.; Sessa, William C.

doi:10.1172/jci119121

Cited by 266 publications

(134 citation statements)

References 45 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…The reasons for this apparent discrepancy are not known, but it might be attributed to various amounts of contaminating cells or may reflect differences in the assays used to detect eNOS. We could not detect iNOS mRNA in PMN challenged with CpG-DNA for up to 4 h. Although iNOS-positive PMN have been shown in tissue samples and exudates (25), at least 16-h exposure of human PMN to LPS or cytokines in vitro is required for iNOS expression (40). Whether CpG-DNA is capable of inducing iNOS expression in PMN after prolonged incubation periods remains to be investigated.…”

Section: Discussionmentioning

confidence: 76%

“…The following primers were used for subsequent PCR analysis: human inducible NOS (iNOS): sense, 5Ј-TCTCTCGGCCAC CTTTGATGAG-3Ј; antisense 5Ј-GGTTGCATCCAGCTTGACCAG-3Ј; human endothelial NOS (eNOS); sense, 5Ј-GTGATGGCGAAGCGAGT GAAG-3Ј; antisense, 5Ј-CCGAGCCCGAACACACAGAAC-3Ј; human neuronal NOS: sense, 5Ј-CTTCTGGCAACAGCGGCAATTTG-3Ј; antisense, 5Ј-TGGACTCAGATCTAAGGCGGTTG-3Ј; and ␤-actin: sense, 5Ј-ATGCCATCCTGCGTCTGGAC-3Ј; antisense, 5Ј-AGCATTTGCG GTGCACGATGG-3Ј (25). The resultant PCR products were 412, 421, 458, and 500 bp, respectively, and were electrophoresed on 1.2% agarose and stained with ethidium bromide.…”

Section: Expression Of No Synthase (Nos) Isoformsmentioning

confidence: 99%

See 1 more Smart Citation

Activation of TLR-9 Induces IL-8 Secretion through Peroxynitrite Signaling in Human Neutrophils

József

Khreiss

Kebir

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Bacterial DNA containing unmethylated CpG motifs is emerging as an important regulator of functions of human neutrophil granulocytes (polymorphonuclear leukocytes (PMN)). These motifs are recognized by TLR-9. Recent studies indicate that peroxynitrite (ONOO−) may function as an intracellular signal for the production of IL-8, one of the key regulators of leukocyte trafficking in inflammation. In this study we investigated whether bacterial DNA (CpG-DNA) could induce ONOO− signaling in human PMN. Human whole blood, isolated PMN (purity, >95%), and high purity (>99%) PMN respond to CpG-DNA, but not to calf thymus DNA, with secretion of IL-8 and, to a lesser extent, IL-6 and TNF. Methylation of cytosines in CpG-DNA resulted in a complete loss of activity. The endosomal acidification inhibitors, bafilomycin A and chloroquine, inhibited CpG-DNA-induced cytokine release from PMN. CpG-DNA-induced IL-8 mRNA expression and release was also blocked by the NO synthase inhibitor Nω-nitro-l-arginine methyl ester. CpG-DNA evoked concomitant increases in intracellular superoxide and NO levels, leading to enhanced ONOO− formation and, consequently, nuclear accumulation of c-Fos and NF-κB. Pharmacological inhibition of NF-κB activation attenuated ∼75% of CpG-DNA-evoked IL-8 release. These results identify ONOO−-dependent activation of NF-κB and c-Fos as an important mechanism that mediates PMN responses, including IL-8 gene expression and release, to bacterial DNA and unmethylated CpG motifs in particular. Enhanced ONOO− formation represents a mechanism by which bacterial DNA may contribute to prolongation and amplification of the inflammatory response.

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Expression Of No Synthase (Nos) Isoformsmentioning

confidence: 99%

Activation of TLR-9 Induces IL-8 Secretion through Peroxynitrite Signaling in Human Neutrophils

József

Khreiss

Kebir

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…There may be several sources of nitrosative stress in the urinary tract during UTI. Host-derived production of NO from iNOS by uroepithelial cells and neutrophils is most likely a major source [25] [24,29]. Indeed, the fact that all urine samples were positive for leukocyte esterase indicates that the host response was activated in the UTI patients.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, detrimental effects of NO and RNI on non-pathogenic E. coli K-12 strains are also well established [3,7,10,22,23]. Studies in humans and mice have shown that urinary neutrophils and urinary tract epithelial cells are able to express iNOS in response to UPEC infection [24,25,26] and NO levels have been documented to increase in the urinary bladder in patients suffering from UTI [27]. Furthermore, infected urine contains nitrite as a result of bacterial nitrate reductase and acidified urine releases NO from nitrite [28].…”

mentioning

confidence: 99%

Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – Implications for urinary tract infection

Svensson

Poljakovic

Säve

et al. 2010

Microbial Pathogenesis

View full text Add to dashboard Cite

Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coliimplications for urinary tract infection. During the course of urinary tract infection (UTI) nitric oxide (NO) is generated as part of host response. The aim of this study was to investigate the significance of the NO-detoxifying enzymes flavohemoglobin (Hmp) and flavorubredoxin (Norv) in protection of uropathogenic Escherichia coli (UPEC) against nitrosative stress. Hmp (J96∆hmp) and norV (J96∆norV) knockout mutants of UPEC strain J96 were constructed using a single-gene deletion strategy. Bacterial tolerance and expression of hmp and norV in response to the NO-donor DETA/NO was evaluated in Luria broth and urine from healthy volunteers. Bacterial NO consumption and respiratory inhibition were assessed when exposed to NO. Expression of hmp and norV from E. coli originating from patients with UTI was evaluated using real-time PCR. The colonizing ability of J96 wild-type (wt) compared to an hmp-deficient mutant was assessed using a competition-based mouse UTI model. The viability of J96∆hmp and J96∆norV was significantly reduced compared to the wildtype strain after exposure to DETA/NO. The hmp expression in DETA/NO-exposed cultures was similar in J96wt and J96∆norV, while J96∆hmp showed an increased norV expression compared to J96wt. The NO consumption in J96∆hmp, but not in J96∆norV, was significantly impaired compared to J96wt. An up-regulation of hmp expression was found in E. coli isolated from all UTIpatients while norV expression increased in 50% of the patients. In the mouse UTI model, the hmp-mutant strain was significantly out-competed by the wild-type strain in the bladder and kidney. Hmp and NorV contribute to the protection of UPEC against NOmediated toxicity in vitro. Screening UPEC isolates from UTI patients revealed an increased hmp expression in all patients which confirms that hmp expression occurs in vivo in the infected human urinary tract. The ability to colonize the mouse urinary tract was impaired in the hmp-deficient mutant compared to the wild-type strain. NO-detoxification by Hmp is suggested to be an important characteristic for UPEC in protection against nitrosative stress and may be a virulence-facilitating factor.

show abstract

“…The few studies that have dealt with iNOS subcellular localization have provided diverse findings. iNOS has been reported to reside in the cell as a diffuse cytosolic protein or to localize in vesicular or perinuclear structures (14)(15)(16). In one study, the perinuclear location was assigned to the Golgi (17).…”

mentioning

confidence: 99%

Regulation of inducible nitric oxide synthase by aggresome formation

Kołodziejska

Burns

Moore

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Misfolding and aggregation of proteins play an important part in the pathogenesis of several genetic and degenerative diseases. Recent evidence suggests that cells have evolved a pathway that involves sequestration of aggregated proteins into specialized ''holding stations'' called aggresomes. Here we show that cells regulate inducible NO synthase (iNOS), an important host defense protein, through aggresome formation. iNOS aggresome formation depends on a functional dynein motor and the integrity of the microtubules. The iNOS aggresome represents a ''physiologic aggresome'' and thus defines a new paradigm for cellular regulation of protein processing. This study indicates that aggresome formation in response to misfolded proteins may merely represent an acceleration of an established physiologic regulatory process for specific proteins whose regulation by aggresome formation is deemed necessary by the cell.

show abstract

Bacterial infection induces nitric oxide synthase in human neutrophils.

Cited by 266 publications

References 45 publications

Activation of TLR-9 Induces IL-8 Secretion through Peroxynitrite Signaling in Human Neutrophils

Activation of TLR-9 Induces IL-8 Secretion through Peroxynitrite Signaling in Human Neutrophils

Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – Implications for urinary tract infection

Regulation of inducible nitric oxide synthase by aggresome formation

Contact Info

Product

Resources

About