The systemic vasculature that perfuses the airway wall is the relevant lung circulation that provides nutrient flow and blood-borne elements to the airway. The bronchial circulation has been viewed as an extensive vascular network lining the airway walls that undergo pathologic conditions, might adversely affect airway patency. Controversy exists as to whether this circulatory bed, through engorgement and edema, can cause physical encroachment on the airway lumen and cause airflow obstruction. Although some experiments evidence substantiates physical modulation of the airway by the bronchial vascular network, little is known about airway vascular endothelial mechanisms that might modulate the airway environment. Chief among these are the effects of blood flow and permeability on inflammatory cell recruitment to the airway. Blood flow-induced stimulation of bronchial endothelium is likely an important mechanisms to control regional perfusion distribution and transit of blood components. Inflammatory cell recruitment to the airway wall is generally assumed to be controlled by airway vascular endothelial adhesion, however, little in vivo data exists to support this assumption. We propose the following HYPOTHESIS: The bronchial vasculature is permissive in allowing airways inflammation and is a major factor controlling the extent of inflammatory cell influx to the airway wall. Since the inflammatory status of the airway wall is thought to dictate both airway size and hyperreactivity, the bronchial circulation is an essential component in this process. In this proposal we explore the interaction between the airway circulation and inflammation.
Specific aims will determine: 1) whether changes in bronchial blood flow, volume, and permeability during an antigen-induced inflammatory condition will cause airway luminal narrowing; the effects of altered airway blood flow, increasing permeability, and induction of endothelial adhesion molecule expression after cytokine and antigen challenge on 2) leukocyte transit through the bronchial vasculature and 3) rolling, adhesion and migration of leukocytes on tracheal post-capillary venules, and 4) inflammatory factors that specifically alter bronchial endothelial permeability and leukocyte migration.
These aims will be performed in a) a sheep model in which the bronchial artery can be cannulated and perfused (Aim 1 & 2); b) rat trachea where individual blood vessel-leukocyte interactions can be monitored using intravital microscopy (Aim 3), and c) sheep bronchial endothelial cell cultures where mechanisms and modulators of permeability and leukocyte transmigration can be determined. The results of the proposed studies will provide new in vivo information regarding the mechanisms of leukocyte recruitment of the airways.

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National Heart, Lung, and Blood Institute (NHLBI)
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