Prospective Respiratory Gated Carbon Nanotube Micro Computed Tomography

Challenges remain in the imaging of the lungs of free-breathing mice. Though computed tomography (CT) is near optimal from a contrast perspective, the rapid respiration rate, limited temporal resolution and inflexible x-ray pulse control of most micro-CT (mCT) scanners limits their utility in pulmonary imaging. Carbon nanotubes (CNTs) have permitted the development of field emission cathodes, with rapid switching and precise pulse control. The goal of this study was to explore the utility of a CNT-based mCT for application in quantitative pulmonary imaging

The role of ecto -5\u27 -nucleotidase (CD73) in lung injury

In response to injury, tissues undergo a specific, coordinated response that results in limitation of injury, debridement of injured tissue, and eventual repair. Although these phases are somewhat overlapping, the regulation of the mediators and effectors of each must be controlled to properly switch from one phase to another. In cases of chronic lung disease, pulmonary injury does not resolve. Instead, inflammatory and repair processes are dysregulated, resulting in further injury, which can cyclically lead to further dysregulated response. The pathways by which this occurs are largely unknown. The signaling nucleoside adenosine potentially occupies an interesting position in the switching of phases of the response, in that it has inflammatory, anti-inflammatory, and profibrotic effects. Elevated levels of adenosine have been associated with lung injury, but it is not known if and how this is regulated. Here, we present data showing that elevated activity of ecto-5\u27-nucleotidase (CD73) activity is correlated with adenosine accumulation in three different models of lung injury. We also show, through the use of mice deficient in CD73, that this elevated nucleotidase activity is necessary for the observed accumulation of adenosine in at least one of these models; bleomycin induced pulmonary inflammation and fibrosis. Furthermore, we show that adenosine is protective in this model, as removal of the capacity to accumulate adenosine results in exacerbation of the pathology of bleomycin challenge. This pathway for adenosine formation shows promise for therapeutic intervention as well, as manipulation of this pathway through administration of exogenous nucleotidase activity displayed antiinflammatory effects. We also show that the regulation of CD73 activity is part of a larger process of purinergic remodeling, in which expression of adenosine receptors and enzymes responsible for metabolism of adenosine and its nucleotides undergo coordinated regulation with the end effect of accumulation of adenosine and altered purinergic signaling upon injury. These data demonstrate that in bleomycin induced pulmonary injury, adenosine is generated via extracellular hydrolysis of adenine nucleotides, that this process is dependent of the activity of CD73, and that the adenosine produced has an overall protective effect, acting to limit tissue damage

A protective role for the A(1) adenosine receptor in adenosine-dependent pulmonary injury

Adenosine is a signaling nucleoside that has been implicated in the regulation of asthma and chronic obstructive pulmonary disease. Adenosine signaling can serve both pro- and anti-inflammatory functions in tissues and cells. In this study we examined the contribution of A(1) adenosine receptor (A(1)AR) signaling to the pulmonary inflammation and injury seen in adenosine deaminase–deficient (ADA-deficient) mice, which exhibit elevated adenosine levels. Experiments revealed that transcript levels for the A(1)AR were elevated in the lungs of ADA-deficient mice, in which expression was localized predominantly to alveolar macrophages. Genetic removal of the A(1)AR from ADA-deficient mice resulted in enhanced pulmonary inflammation along with increased mucus metaplasia and alveolar destruction. These changes were associated with the exaggerated expression of the Th2 cytokines IL-4 and IL-13 in the lungs, together with increased expression of chemokines and matrix metalloproteinases. These findings demonstrate that the A(1)AR plays an anti-inflammatory and/or protective role in the pulmonary phenotype seen in ADA-deficient mice, which suggests that A(1)AR signaling may serve to regulate the severity of pulmonary inflammation and remodeling seen in chronic lung diseases by controlling the levels of important mediators of pulmonary inflammation and damage