LOADING WITH OXIDIZED LOW-DENSITY-LIPOPROTEIN ALTERS ENDOCYTIC AND SECRETORY ACTIVITIES OF MURINE MACROPHAGES

Lipid-loaded macrophages were produced in vitro by incubation with ace tylated or copper-oxidized LDL. In order to establish whether cellular membrane traffic is generally perturbed by such loading, we assessed endocytosis of fluid; cell surface binding, internalisation and degrad ation of a soluble ligand and of a particulate preparation; and exocyt osis of lysosmal enzymes. Fluid-phase pinocytosis of sucrose was unaff ected by either form of loading, Binding, uptake and degradation of so luble (mannosylated-BSA) and particulate (zymosan) ligands by these li pid-loaded and by non-loaded cells were compared. Loading with oxidize d LDL decreased the processing of both ligands, while loading with ace tylated LDL had little effect. Loading with oxidized LDL (Ox-LDL) also decreased zymosan binding at 4 degrees C; and thr: internalisation an d degradation of ligands in Ox-LDL loaded and non-loaded cells reflect ed the extent of surface binding. Changes in binding and uptake of man nosylated-BSA and zymosan were not due to changes in viability or cell number. Zymosan stimulated release of lysosomal beta-N-acetyl-D-gluco saminidase from the cells. Loading with Ox- but not Ac-LDL decreased b eta-Nacetyl-D-glucosaminidase secretion. After incubation with zymosan , intracellular levels of the enzyme were increased in the Ox-LDL load ed cells. Zymosan uptake and beta-N-acetpl-D-glucosaminidase secretion were correlated, but enzyme activity per culture rose more in the abs ence than in the presence of zymosan, We conclude that membrane traffi c is perturbed in model foam cells, particularly those loaded with Ox- LDL.