Degradation of chylomicron remnants by macrophages occurs via phagocytosis.
Chylomicron remnants bound to rabbit alveolar macrophages with high-affinity (Kd = 3.3 +/- 0.71 microgram of protein/mL). The binding of chylomicron remnants was competitively inhibited in the presence of unlabeled remnants and to a lesser extent by unlabeled low-density lipoproteins. Pretreatment of cells with either trypsin or pronase inhibited degradation in a dose and time dependent manner, suggesting involvement of a cell surface protein. Chylomicron remnants were degraded by alveolar macrophages from Watanabe heritable hyperlipidemic (WHHL) rabbits, which are devoid of LDL receptor activity. Moreover, colchicine and monensin which are endocytotic and lysozomal inhibitors, respectively, did not have any effect on the degradation of chylomicron remnants by macrophages from normal rabbits. The absence of divalent cations was found to enhance chylomicron remnant degradation by macrophages. Activated alpha 2-macroglobulin and lactoferrin had no effect on chylomicron remnant degradation, indicating that the low-density lipoprotein receptor-related protein was not involved. In addition, the scavenger receptor inhibitors polyinosinic acid and fucoidan increased degradation of chylomicron remnant-ruling out uptake as a consequence of lipoprotein modification. Rather, the phagocytotic inhibitor cytochalasan D was found to significantly decrease chylomicron remnant degradation. Collectively, our data show that chylomicron remnants are metabolized by phagocytotic pathways initiated after binding to a cell surface protein which is distinct from the LDL receptor, LRP, or scavenger receptors.
Mamo
J C
JC
Department of Physiology, University of Western Australia.
Elsegood
C L
CL
Gennat
H C
HC
Yu
K
K
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D002914:Chylomicrons / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D010450:Endopeptidases / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000503:physiopathology*; D007700:Kinetics; D007781:Lactoferrin / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000302:isolation & purification / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000502:physiology*; D008985:Monensin / Q000494:pharmacology; D010587:Phagocytosis; D011817:Rabbits; D012016:Reference Values; D000511:alpha-Macroglobulins / Q000494:pharmacology
D002914:Chylomicrons; D008077:Lipoproteins, LDL; D000511:alpha-Macroglobulins; D008985:Monensin; D004492:Edetic Acid; D010450:Endopeptidases; D007781:Lactoferrin; D003078:Colchicine