Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity.

Fang, Ferric C.

doi:10.1172/jci119473

Cited by 1,042 publications

(726 citation statements)

References 71 publications

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“…As previously stated, one of the most important functions of NO in the immune system is in antimicrobial defence (De Groote & Fang 1995, Fang 1997, Nathan & Shiloh 2000. Reactive oxygen and nitrogen species derived from NO are essential for protection against various intracellular pathogens including viruses, bacteria, fungi and protozoans.…”

Section: No and The Immune Responsementioning

confidence: 99%

The effects of nitric oxide on the immune system during Trypanosoma cruzi infection

Gutierrez

Mineo

Pavanelli

et al. 2009

Mem. Inst. Oswaldo Cruz

109

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Section: No and The Immune Responsementioning

confidence: 99%

The effects of nitric oxide on the immune system during Trypanosoma cruzi infection

Gutierrez

Mineo

Pavanelli

et al. 2009

Mem. Inst. Oswaldo Cruz

109

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“…ROS, including free radicals, oxygen ions, and peroxides, have also been implicated in cell damage like NO (56,57). ROS is known to contribute to the efficiency of parasite killing (57,58). This led to the determination of nitrite and ROS levels in vaccinated vs control mice 8 wk after infection.…”

Section: Measurement Of No and Ros In Immunized Mice Challenged Withmentioning

confidence: 99%

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Sharma

Madhubala

2009

The Journal of Immunology

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Resistance of Leishmania donovani to sodium antimony gluconate has become a critical issue in the current, prolonged epidemic in India. Hence, there is an urgent need for a vaccine that is protective against both antimony-susceptible and -resistant strains of L. donovani. The multigene LD1 locus located on chromosome 35 of Leishmania is amplified in ∼15% of the isolates examined. The open reading frame F (ORFF), a potential vaccine candidate against visceral leishmaniasis, is part of the multigene LD1 locus. ORFF was expressed as a chimeric conjugate of ubiquitin to elicit an Ag-specific cell-mediated immune response. Analysis of the cellular immune responses of ubiquitin-conjugated ORFF (UBQ-ORFF) DNA-immunized, uninfected BALB/c mice demonstrated that the vaccine induced enhanced IFN-γ-producing CD4+ and CD8+ T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-γ and the low levels of IL-4 and IL-10 further indicated that the immune responses with UBQ-ORFF were mediated toward the Th1 rather than Th2 type. Infection of immunized mice with either the antimony-susceptible (AG83) or -resistant (GE1F8R) L. donovani strain showed that UBQ-ORFF DNA vaccine induced higher protection when compared with ORFF DNA. UBQ-ORFF DNA-immunized and -infected mice showed a significant increase in IL-12 and IFN-γ and significant down-regulation of IL-10. High levels of production of nitrite and superoxide, two macrophage-derived oxidants that are critical in controlling Leishmania infection, were observed in protected mice. The feasibility of using ubiquitinated-conjugated ORFF DNA vaccine as a promising immune enhancer for vaccination against both antimony-susceptible and -resistant strains of L. donovani is reported.

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“…Nitric oxide (NO) is a free radical with multiple and diverse biological functions (1)(2)(3)(4)(5). Interactions of NO with Fe-protoporphyrin in heme proteins are of great physiological importance (1).…”

mentioning

confidence: 99%

NO Binding Induced Conformational Changes in a Truncated Hemoglobin from Mycobacterium tuberculosis

Mukai

Ouellet

et al. 2004

Biochemistry

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The resonance Raman spectra of the NO-bound ferric derivatives of wild-type HbN and the B10 Tyr f Phe mutant of HbN, a hemoglobin from Mycobacterium tuberculosis, were examined with both Soret and UV excitation. The Fe-N-O stretching and bending modes of the NO derivative of the wild-type protein were tentatively assigned at 591 and 579 cm -1 , respectively. Upon B10 mutation, the Fe-NO stretching mode was slightly enhanced and the bending mode diminished in amplitude. In addition, the N-O stretching mode shifted from 1914 to 1908 cm -1 . These data suggest that the B10 Tyr forms an H-bond(s) with the heme-bound NO and causes it to bend in the wild-type protein. To further investigate the interaction between the B10 Tyr and the heme-bound NO, we examined the UV Raman spectrum of the B10 Tyr by subtracting the B10 mutant spectrum from the wild-type spectrum. It was found that, upon NO binding to the ferric protein, the Y 8a mode of the B10 Tyr shifted from 1616 to 1622 cm -1 , confirming a direct interaction between the B10 Tyr and the heme-bound NO. Furthermore, the Y 8a mode of the other two Tyr residues at positions 16 and 72 that are remote from the heme was also affected by NO binding, suggesting that NO binding to the distal site of the heme triggers a large-scale conformational change that propagates through the pre-F helix loop to the E and B helices. This large-scale conformational change triggered by NO binding may play an important role in regulating the ligand binding properties and/or the chemical reactivity of HbN.

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Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity.

Cited by 1,042 publications

References 71 publications

The effects of nitric oxide on the immune system during Trypanosoma cruzi infection

The effects of nitric oxide on the immune system during Trypanosoma cruzi infection

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

NO Binding Induced Conformational Changes in a Truncated Hemoglobin from Mycobacterium tuberculosis

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