SWR Mice Are Highly Susceptible to Pulmonary Infection with Mycobacterium tuberculosis

ABSTRACT Inbred mice differ in their abilities to control the growth of Mycobacterium tuberculosis in the lung and can as a result be regarded as either resistant or susceptible strains. In this study we report that the SWR mouse is both highly susceptible and in addition appears incapable of establishing a characteristic state of chronic disease after low-dose aerosol infection. In comparison to C57BL/6 mice, SWR mice were unable to contain the bacterial load in the lungs, resulting in progressive fatal disease. Histologic analysis of the lung tissue revealed evidence of a florid inflammatory cell response in the SWR mice leading to degeneration and necrosis and consolidation of a large percentage of the lung surface area. Digestion of infected lungs and analysis by flow cytometry demonstrated an initially similar but eventually higher number of lymphocytes accumulating in the SWR mice. Additionally, in contrast to the C57BL/6 mice, SWR mice had a significantly lower percentage of CD4 T cells in the lungs showing evidence of proliferation and positive intracellular staining for gamma interferon during the first two months of infection, and a lower percentage of both CD4 and CD8T cells exhibiting differentiation to an effector/memory phenotype during the first month of infection. We propose that further investigation of the SWR mouse may provide a new animal model for immunocompetent individuals apparently unable to effectively control the growth of M. tuberculosis in the lung.

Effect of common vasodilators on lung microvascular permeability

The effect of papaverine on the albumin permeability-surface area product (PS), reflection coefficient (sigma), and capillary filtration coefficient (Kf) was examined in isolated rabbit lungs. Because PS and Kf are functions of vascular surface area and permeability, we also compared papaverine with two other means of maximizing lung surface area: isoproterenol (1 x 10(-7) M) and a mild increase in vascular pressure. Only lungs perfused with 0.1 mg/ml papaverine were significantly different from control. PS increased from control (2.80 +/- 0.16 to 5.53 +/- 0.20 ml.min-1.g dry lung-1 x 10(-2), whereas sigma decreased from control (0.92 +/- 0.01 to 0.78 +/- 0.03). Kf after papaverine was significantly lower than baseline predrug Kf (5.60 +/- 0.78 to 4.56 +/- 0.53 ml.s-1.cmH2O-1.g dry lung-1 x 10(-3). However, this group's predrug Kf was higher than that of any other group. Our results indicate that papaverine increases albumin permeability and decreases endothelial selectivity. The isolated perfused lung appears fully recruited, because Kf and PS did not increase with isoproterenol or increased vascular pressure. Papaverine should be used with caution in the Ringer-perfused lung.