Increased Mast Cell Density and Airway Responses to Allergic and Non-Allergic Stimuli in a Sheep Model of Chronic Asthma

BACKGROUND: Increased mast cell (MC) density and changes in their distribution in airway tissues is thought to contribute significantly to the pathophysiology of asthma. However, the time sequence for these changes and how they impact small airway function in asthma is not fully understood. The aim of the current study was to characterise temporal changes in airway MC density and correlate these changes with functional airway responses in sheep chronically challenged with house dust mite (HDM) allergen. METHODOLOGY/PRINCIPAL FINDINGS: MC density was examined on lung tissue from four spatially separate lung segments of allergic sheep which received weekly challenges with HDM allergen for 0, 8, 16 or 24 weeks. Lung tissue was collected from each segment 7 days following the final challenge. The density of tryptase-positive and chymase-positive MCs (MC(T) and MC(TC) respectively) was assessed by morphometric analysis of airway sections immunohistochemically stained with antibodies against MC tryptase and chymase. MC(T) and MC(TC) density was increased in small bronchi following 24 weeks of HDM challenges compared with controls (P<0.05). The MC(TC)/MC(T) ratio was significantly increased in HDM challenged sheep compared to controls (P<0.05). MC(T) and MC(TC) density was inversely correlated with allergen-induced increases in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05). MC(T) density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01). CONCLUSIONS: MC(T) and MC(TC) density in the small airways correlates with better lung function in this sheep model of chronic asthma. Whether this finding indicates that under some conditions mast cells have protective activities in asthma, or that other explanations are to be considered requires further investigation

Measurement of sound speed vs. depth in South Pole ice for neutrino astronomy

We have measured the speed of both pressure waves and shear waves as a function of depth between 80 and 500 m depth in South Pole ice with better than 1% precision. The measurements were made using the South Pole Acoustic Test Setup ({SPATS}), an array of transmitters and sensors deployed in the ice at South Pole Station in order to measure the acoustic properties relevant to acoustic detection of astrophysical neutrinos. The transmitters and sensors use piezoceramics operating at $\sim$5-25 kHz. Between 200 m and 500 m depth, the measured profile is consistent with zero variation of the sound speed with depth, resulting in zero refraction, for both pressure and shear waves. We also performed a complementary study featuring an explosive signal propagating from 50 to 2250 m depth, from which we determined a value for the pressure wave speed consistent with that determined with the sensors operating at shallower depths and higher frequencies. These results have encouraging implications for neutrino astronomy: The negligible refraction of acoustic waves deeper than 200 m indicates that good neutrino direction and energy reconstruction, as well as separation from background events, could be achieved.Comment: 14 pages, 7 figure