CLEARANCE OF SURFACTANT-LIKE PARTICLE PROTEINS FROM CIRCULATION IN RATS

Surfactant-like particles (SLP) have been isolated from the apical surface of rat enterocytes but appear to arise within the enterocyte and to be secreted into neighboring lymphatics (K. DeSchryver-Kecskemeti, R. Eliakim, S. Carroll, W. F. Stenson, M. A. Moxley, and D. H. Alpers. J. Clin. Invest. 84: 1355-1361, 1989). The present study was undertaken to analyze the clearance and distribution of these particle-associated proteins in vivo in the rat. Labeling of particles isolated from apical scrapings of rat enterocytes with I-125 enabled identification of proteins of 116, 92, 68, 58, 48, 31, and 25 kDa. After the intravenous administration of I-125-SLP, th, trichloroacetic acid-precipitable radioactivity in the plasma disappeared in a biphasic pattern. The average half-life of the early phase was 7.5 min and the second phase was 75 min. The half-life of a subset of the proteins (116, 92, and 48 kDa) was shorter, measuring 4.5 min for the first phase and ranging from 20 to 52 min for the second phase. The amounts of labeled particle distributed to the liver, kidney, and spleen were much greater than could be accounted for by distribution in the extracellular space alone. The liver accounted for removal of similar to 50% of label in the first phase, with the kidney and spleen contributing 10 and 1%, respectively. Only 0.5 and 2.5% of labeled protein appeared in the bile and urine, respectively. The majority of labeled protein remaining in the serum after the initial phase of tissue uptake migrated at a density of 1.07-1.08, characteristic of intact particles, but slowly shifted to higher densities over 24 h. The maximum binding capacity was 56 nmol/mg membrane protein (Michaelis constant = 51 pM) using hepatic basolateral membranes. The particle was taken up into hepatocytes, as demonstrated by autoradiography. These data demonstrate the importance of the liver in clearing SLP from the blood in rats. The slow clearance of a portion of the particle protein provides support for the continued presence of these proteins in the serum of rats.