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 diffe rent rates, but the underlying mechanism for this effect has not been resolved. To investigate the differences in clearance rates between sm all and large particles, chylomicron-like lipid emulsions labeled with radioactive triolein and cholesteryl oleate were injected into consci ous rats. The clearance from plasma of small emulsion particles was si gnificantly slower than large when equal lipid masses of small and lar ge particles were injected. Similar results were obtained in clearance studies with lymph chylomicrons. When equal numbers of either either small or large emulsion particles were injected into rats, the clearan ce of the triolein label from large particles nas significantly slower than small particles, but no significant difference nas found in the clearance of the remnants (traced by the cholesteryl oleate label) der ived from small and large particles. However, when increased numbers o f either small or large particles were injected, the clearances of emu lsion triolein and remnants were significantly decreased. Larger parti cles were found to be lipolyzed significantly less than small. Simulta neous injections showed competition for removal of large and small par ticles, suggesting competition for a common, saturable removal process . Our findings provide evidence that particle number and size are dete rminants of the rates of plasma clearance of the triglyceride-rich lip oproteins and the results are consistent with a saturable process. Our data also show that particle number is more important than size and h igher numbers of particles markedly affect the clearance of triglyceri de-rich lipoproteins. However particle uptake by the liver is not sens itive to remnant size.