Effects of particle size and number on the plasma clearance of chylomicrons and remnants.

Lymph chylomicrons of different sizes are known to be cleared at different rates, but the underlying mechanism for this effect has not been resolved. To investigate the differences in clearance rates between small and large particles, chylomicron-like lipid emulsions labeled with radioactive triolein and cholesteryl oleate were injected into conscious rats. The clearance from plasma of small emulsion particles was significantly slower than large when equal lipid masses of small and large particles were injected. Similar results were obtained in clearance studies with lymph chylomicrons. When equal numbers of either small or large emulsion particles were injected into rats, the clearance of the triolein label from large particles was significantly slower than small particles but no significant difference was found in the clearance of the remnants (traced by the cholesteryl oleate label) derived from small and large particles. However, when increased numbers of either small or large particles were injected, the clearances of emulsion triolein and remnants were significantly decreased. Larger particles were found to be lipolyzed significantly less than small. Simultaneous injections showed competition for removal of large and small particles, suggesting competition for a common, saturable removal process. Our findings provide evidence that particle number and size are determinants of the rates of plasma clearance of the triglyceride-rich lipoproteins and the results are consistent with a saturable process. Our data also show that particle number is more important than size and higher numbers of particles markedly affect the clearance of triglyceride-rich lipoproteins. However particle uptake by the liver is not sensitive to remnant size.