PARTITIONING LUNG AND PLASMA PROTEINS: CIRCULATING SURFACTANT PROTEINS AS BIOMARKERS OF ALVEOLOCAPILLARY PERMEABILITY^‡

Abstract

1. The alveolocapillary membrane faces an extraordinary task in partitioning the plasma and lung hypophase proteins, with a surface area approximately 50-fold that of the body and only 0.1-0.2 micron thick. 2. Lung permeability is compromised under a variety of circumstances and the delineation between physiological and pathological changes in permeability is not always clear. Although the tight junctions of the epithelium, rather than the endothelium, are regarded as the major barrier to fluid and protein flux, it is becoming apparent that the permeability of both are dynamically regulated. 3. Whereas increased permeability and the flux of plasma proteins into the alveolar compartment has dire consequences, fortuitously the flux of surfactant proteins from the airspaces into the circulation may provide a sensitive means of non-invasively 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 concentration gradients (approximately 1:1500-7000) into the circulation in a manner that reflects lung function and injury score. Surfactant proteins vary markedly in size (approximately 20-650 kDa) and changes in the relative amounts appear particularly diagnostic with regard to disease severity. Alveolar levels of surfactant proteins remain remarkably constant despite respiratory disease 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.

Anti-KC Autoantibody:KC Complexes Cause Severe Lung Inflammation in Mice via IgG Receptors

“…Lack of a difference in albumin concentrations between WT/LPS and WT/Sal mice agrees with previously reported finding in mice treated with intraperitoneal LPS (31). However, albumin may sometimes not reflect adequately changes in permeability (33). Therefore, we measured total protein concentrations in lavage samples.…”

Serum levels of CC16, SP-A and SP-B reflect tobacco-smoke exposure in asymptomatic subjects

“…Basolateral secretion of CC16, SP-A or SP-B has never been described and nonetheless, lung lymph accounts for only y25% of total lung protein clearance from the interstitium [29]. Consistent with this, the current authors have previously estimated that, at least in respect to SP-A and -B, pleural concentrations and rates of lymph flow are insufficient to account for the relative concentration changes that occur in these proteins in the circulation [30]. Tobacco smoking decreases lung levels of CC16 [3,31,32] and may explain, at least in part, the reduced levels of this protein in the circulation of the smokers in this study.…”

Contribution of Human Lung Parenchyma and Leukocyte Influx to Oxidative Stress and Immune System-Mediated Pathology following Nipah Virus Infection

“…NiV-B-induced multinucleated cells were found in the bronchiolar interstitium, as previously shown for human lung grafts (11,15). The 10-fold increase in the level of human pulmonary SP-D in sera of mice also suggested increases in alveolar-capillary permeability and alveolar damage of the human lung grafts and was previously considered, when detected in the human bloodstream, a hallmark of ALI (42,43). In addition, NiV-B infected the endothelial lining of the lung vasculature, which is one of the main cellular targets for henipaviruses (14,44) and where edema, fibrinoid necrosis, and thrombus formation were observed in the vicinity, suggesting vasculitis.…”