Interstitial fluid dynamics, macromolecular structure and morphology in interstitial lung edema

摘要

Pulmonary function relies on the maintenance of a "dry" interstitial tissue as indicated by the fact that interstitial fluid pressure (Pip) is much lower in lung parenchyma, about - 10 cm H{sub}2O [1], compared with other tissues in control conditions. To minimize interstitial fluid volume, the lung requires 1) a selective endothelial barrier limiting capillary to interstitium fluid filtration and restricting plasma protein escape [2], 2) an efficient interstitial fluid drainage provided by pulmonary lymphatics, and 3) a very low tissue matrix compliance that depends mainly on the macromolecular organization of extracellular matrix (ECM). All these features add to provide a strong "tissue safety factor" that limits edema formation. The ECM of lung interstitium provides a strong and expandable framework for the thin alveolar-capillary intersection and consists mainly of collagen, elastic fibers and proteoglycans which are largely responsible for tensile strength, elastic recoil and tissue compliance. The integrity of the ECM native architecture depends on the balance between the regulation of synthesis and degradation of its components. This article summarizes data from a series of studies aimed at elucidating the initial sequence of events leading to the development of pulmonary edema. These studies were based on an experimental animal model (rabbits) that allowed us to induce a relatively small and controlled perturbation of the physiological interstitial fluid dynamics. We will therefore describe the alterations in microvascular- interstitial fluid exchanges in terms of macromolecular derangement of ECM, focusing in particular on the role of proteoglycans that are essential for structural matrix integrity. We will then relate the biochemical changes to modification in tissue morphology.