8 research outputs found
Effects of Mycobacterium bovis BCG Infection on Regulation of l-Arginine Uptake and Synthesis of Reactive Nitrogen Intermediates in J774.1 Murine Macrophages
The generation of nitric oxide (NO) by activated macrophages is believed to control mycobacterial infection in the murine system. In this study we examined the effect of Mycobacterium bovis BCG infection on the l-arginine-dependent NO pathway in J774.1 murine macrophages. We have confirmed previous results by demonstrating that stimulation of J774.1 with lipopolysaccharide (LPS) and gamma interferon (IFN-γ) results in an increase in the uptake of (3)H-labeled l-arginine and a concomitant increase in the production of NO. We have also shown that BCG can mimic LPS treatment, leading to enhanced l-[(3)H]arginine uptake by IFN-γ-stimulated macrophages. Lipoarabinomannan, a component of the BCG cell wall that is structurally similar to LPS, is not responsible for the uptake stimulation in IFN-γ stimulated macrophages. Although we demonstrated that there was a 2.5-fold increase in NO production by macrophages 4 h after LPS–IFN-γ stimulation, BCG infection (with or without IFN-γ stimulation) did not lead to the production of NO by the macrophages by 4 h postinfection. At 24 h postinfection, the infected macrophages that were stimulated with IFN-γ produced amounts of NO similar to those of macrophages stimulated with LPS–IFN-γ. This suggests that there are multiple regulatory pathways involved in the production of NO. Finally, our data suggest that increased expression of the arginine permease, MCAT2B, after 4 h of LPS–IFN-γ treatment or BCG infection–IFN-γ treatment is not sufficient to account for the increases in l-[(3)H]arginine uptake detected. This suggests that the activity of the l-arginine transporter(s) is also altered in response to macrophage activation
Recommended from our members
Report of the APS Neutrino Study Reactor Working Group
The worldwide program to understand neutrino oscillations and determine the neutrino mixing parameters, CP violating effects, and mass hierarchy will require a broad combination of measurements. The group believes that a key element of this future neutrino program is a multi-detector neutrino experiment (with baselines of {approx} 200 m and {approx} 1.5 km) with a sensitivity of sin{sup 2} 2{theta}{sub 13} = 0.01. In addition to oscillation physics, the reactor experiment may provide interesting measurements of sin{sup 2} {theta}{sub W} at Q{sup 2} = 0, neutrino couplings, magnetic moments, and mixing with sterile neutrino states. {theta}{sub 13} is one of the twenty-six parameters of the standard model, the best model of electroweak interactions for energies below 100 GeV and, as such, is worthy of a precision measurement independent of other considerations. A reactor experiment of the proposed sensitivity will allow a measurement of {theta}{sub 13} with no ambiguities and significantly better precision than any other proposed experiment, or will set limits indicating the scale of future experiments required to make progress. Figure 1 shows a comparison of the sensitivity of reactor experiments of different scales with accelerator experiments for setting limits on sin{sup 2} 2{theta}{sub 13} if the mixing angle is very small, or for making a measurement of sin{sup 2} 2{theta}{sub 13} if the angle is observable. A reactor experiment with a 1% precision may also resolve the degeneracy in the {theta}{sub 23} parameter when combined with long-baseline accelerator experiments. In combination with long-baseline measurements, a reactor experiment may give early indications of CP violation and the mass hierarchy. The combination of the T2K and Nova long-baseline experiments will be able to make significant measurements of these effects if sin{sup 2} 2{theta}{sub 13} > 0.05 and with enhanced beam rates can improve their reach to the sin{sup 2} 2{theta}{sub 13} > 0.02 level. If {theta}{sub 13} turns out to be smaller than these values, one will need other strategies for getting to the physics. Thus, an unambiguous reactor measurement of {theta}{sub 13} is an important ingredient in planning the strategy for the future neutrino program
Recommended from our members
Report of the APS Neutrino Study Reactor Working Group
The worldwide program to understand neutrino oscillations and determine the neutrino mixing parameters, CP violating effects, and mass hierarchy will require a broad combination of measurements. The group believes that a key element of this future neutrino program is a multi-detector neutrino experiment (with baselines of {approx} 200 m and {approx} 1.5 km) with a sensitivity of sin{sup 2} 2{theta}{sub 13} = 0.01. In addition to oscillation physics, the reactor experiment may provide interesting measurements of sin{sup 2} {theta}{sub W} at Q{sup 2} = 0, neutrino couplings, magnetic moments, and mixing with sterile neutrino states. {theta}{sub 13} is one of the twenty-six parameters of the standard model, the best model of electroweak interactions for energies below 100 GeV and, as such, is worthy of a precision measurement independent of other considerations. A reactor experiment of the proposed sensitivity will allow a measurement of {theta}{sub 13} with no ambiguities and significantly better precision than any other proposed experiment, or will set limits indicating the scale of future experiments required to make progress. Figure 1 shows a comparison of the sensitivity of reactor experiments of different scales with accelerator experiments for setting limits on sin{sup 2} 2{theta}{sub 13} if the mixing angle is very small, or for making a measurement of sin{sup 2} 2{theta}{sub 13} if the angle is observable. A reactor experiment with a 1% precision may also resolve the degeneracy in the {theta}{sub 23} parameter when combined with long-baseline accelerator experiments. In combination with long-baseline measurements, a reactor experiment may give early indications of CP violation and the mass hierarchy. The combination of the T2K and Nova long-baseline experiments will be able to make significant measurements of these effects if sin{sup 2} 2{theta}{sub 13} > 0.05 and with enhanced beam rates can improve their reach to the sin{sup 2} 2{theta}{sub 13} > 0.02 level. If {theta}{sub 13} turns out to be smaller than these values, one will need other strategies for getting to the physics. Thus, an unambiguous reactor measurement of {theta}{sub 13} is an important ingredient in planning the strategy for the future neutrino program