DEGRADATION OF CHYLOMICRON REMNANTS BY MACROPHAGES OCCURS VIA PHAGOCYTOSIS

Chylomicron remnants bound to rabbit alveolar macrophages with high-af finity (K-d = 3.3 +/- 0.71 mu g of protein/mL). The binding of chylomi cron 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 degra dation 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, wh ich are devoid of LDL receptor activity. Moreover, colchicine and mone nsin which are endocytotic and lysozomal inhibitors, respectively, did not have any effect on the degradation of chylomicron remnants by mac rophages from normal rabbits. The absence of divalent cations was foun d to enhance chylomicron remnant degradation by macrophages. Activated alpha 2-macroglobulin and lactoferrin had no effect on chylomicron re mnant degradation, indicating that the low-density lipoprotein recepto r-related protein was not involved. in addition, the scavenger recepto r inhibitors polyinosinic acid and fucoidan increased degradation of c hylomicron remnant-ruling out uptake as a consequence of Lipoprotein m odification Rather, the phagocytotic inhibitor cytochalasan D was foun d to significantly decrease chylomicron remnant degradation. Collectiv ely, our data show that chylomicron remnants are metabolized by phagoc ytotic pathways initiated after binding to a cell surface protein whic h is distinct from the LDL receptor, LRP, or scavenger receptors.