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Regulation of Mononuclear Inflammation in the Lung by Intercommunications Between the Bronchial and Pulmonary Microcirculations |
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Back to 86th Annual Meeting Back to Program Outline Objective: The development of pulmonary inflammation defines a tradeoff between the need for efficient gas exchange (optimized ventilation-perfusion matching) and the requirement for inflammatory cell delivery to the peripheral site of inflammation. We studied a murine model of acute mononuclear inflammation to define the functional and morphologic adaptive changes in the peripheral lung microcirculation. Methods: To identify microcirculatory adaptations, we studied the pulmonary and bronchial microcirculations in a murine model of acute cellular inflammation induced by the intratracheal instillation of trinitrobenzene sulfonate (TNBS) (n=50). The time course of cellular inflammation was assessed clinically, histologically and functionally. At the peak of inflammation, respiratory mechanics and lung function testing was performed using the Flexivent (SciReq, Montreal) System. The morphology of the inflammatory microcirculation was demonstrated using corrosion casting, 3-D scanning electron microscopy (SEM), and differential microsphere (15um) occlusion. Results: TNBS-treated mice demonstrated a progressive decline in total body weight over 96 hours (p<.001) followed by gradual return of body weight. Serial histologic evaluation mirrored the clinical findings with the peak of mononuclear cell infiltration mapped to the distal bronchioles 96 hours after TNBS instillation. Immunohistochemistry of the infiltrating cells demonstrated both CD4+ and CD11b+ cell populations. Respiratory mechanics demonstrated significantly decreased static (CRS, ST) and dynamic (CL, DYN) pulmonary compliance (p<.001) and increased airway resistance (RAW) (p<.001).Corrosion casting and 3-D SEM of the pulmonary microcirculation demonstrated evidence of increased alveolar capillary permeability, but few adaptive changes distal to the 100um regulatory arteriole. In contrast, differential microsphere occlusion of the two microcirculations demonstrated morphologic and functional evidence of enhanced intercommunications between the bronchial and pulmonary microcirculations at the level of the distal bronchiole. Further, SEM demonstrated possible structural adaptations in the bronchial microcirculation at the level of these pulmonary-systemic anastomoses. Conclusions: These results suggest that the balance between efficient gas-exchange (perfusion matching) and the delivery of inflammatory cells is regulated at the level of the bronchiolar microcirculation. The enhanced intercommunication between systemic and bronchial microcirculations suggests that these anastomoses play a critical regulatory role in the development of mononuclear inflammation in the lung. Back to 86th Annual Meeting Back to Program Outline |
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