Lipoproteins and apolipoproteins in peripheral lymph of normal and cholesterol-fed dogs.
Prenodal peripheral lymph was used as a model of interstitial fluid to obtain information on the composition of lipoproteins and apolipoproteins which are in direct contact with peripheral cells. Lipoproteins resembling plasma lipoproteins in size and electrophoretic mobility were present in the prenodal peripheral lymph of control as well as cholesterol-fed dogs. Most of the lipoproteins in control dogs were high density lipoproteins, both in the plasma and in the lymph. Cholesterol feeding resulted in an increased concentration of lipoprotein particles with decreased electrophoretic mobility (beta-VLDL and, in plasma, HDLc) and decreased concentration of HDL, both in plasma and in lymph. Size distribution of lipoproteins was also markedly altered by cholesterol feeding; most of the lipoproteins were present as IDL and VLDL both in plasma and in lymph. Judged by agarose gel chromatography, the size of the lymph HDL as consistently larger than plasma HDL in both groups of dogs. Furthermore, it appears that cholesterol feeding increased the size of an HDL subfraction, partially resolved by agarose chromatography, both in lymph and plasma. All apolipoproteins present in plasma were also present in lymph. Cholesterol feeding resulted in 3-10-fold increases in plasma apo B, E, and A-IV while apo A-I was drastically decreased. These changes were reflected in lymph to different degrees depending on the size of the lipoprotein fraction containing the individual apolipoproteins. Our findings provide direct evidence that the large, cholesterol-rich, 'atherogenic' lipoproteins found in the plasma of cholesterol-fed dogs (beta-VLDL) are also present in the interstitial fluid and presumably interact with peripheral cells. Our studies furthermore suggest modification of plasma HDL by peripheral cells and/or de novo assembly of an HDL subfraction. The utilization of this animal model may thus provide a direct approach to the study of the interaction of lipoproteins with peripheral cells.