Partitioning lung and plasma proteins: Circulating surfactant proteins as biomarkers of alveolocapillary permeability

1. The alveolocapillary membrane faces an extraordinary task in partitionin g the plasma and lung hypophase proteins, with a surface area approximately 50-fold that of the body and only 0.1-0.2 mu m thick. 2. Lung permeability is compromised under a variety of circumstances and th e delineation between physiological and pathological changes in permeabilit y is not always clear. Although the tight junctions of the epithelium, rath er than the endothelium, are regarded as the major barrier to fluid and pro tein flux, it is becoming apparent that the permeability of both are dynami cally regulated. 3. Whereas increased permeability and the flux of plasma proteins into the alveolar compartment has dire consequences, fortuitously the flux of surfac tant proteins from the airspaces into the circulation may provide a sensiti ve means of noninvasively monitoring the lung, with important implications for treatment modalities. 4. Surfactant proteins are unique in that they are present in the alveolar hypophase in high concentrations. They diffuse down their vast concentratio n gradients (approximately 1:1500-7000) into the circulation in a manner th at reflects lung function and injury score. Surfactant proteins vary marked ly in size (approximately 20-650 kDa) and changes in the relative amounts a ppear particularly diagnostic with regard to disease severity. Alveolar lev els of surfactant proteins remain remarkably constant despite respiratory d isease and, unlike the flux of plasma proteins into the alveolus, which may reach equilibrium in acute lung injury, the flux of surfactant proteins is unidirectional because of the concentration gradient and because they are rapidly cleared from the circulation. 5. Ultimately, the diagnostic usefulness of surfactant proteins as markers of alveolocapillary permeability will demand a sound understanding of their kinetics through the vascular compartment.