EXTRACELLULAR MAST-CELL GRANULES CARRY APOLIPOPROTEIN B-100-CONTAINING LIPOPROTEINS INTO PHAGOCYTES IN HUMAN ARTERIAL INTIMA - FUNCTIONAL COUPLING OF EXOCYTOSIS AND PHAGOCYTOSIS IN NEIGHBORING CELLS

In experimental studies in vitro, mast cells have induced uptake of apolipoprotein B-100 (apoB-100)-containing low-density lipoproteins by macrophages, with the subsequent formation of foam cells, the hallmarks of atherosclerosis. Recently, increased numbers of activated, ie, degranulated, mast cells were found to be present in human coronary fatty streaks and atheromas. We therefore sought evidence of a connection between mast cells and foam cell formation in vivo. In electron microscopic studies of human aortic and coronary fatty streaks and atheromas, exocytosed cytoplasmic secretory granules of mast cells were detected in the vicinity of their parent cells. These exocytosed granules had bound apoB-100-containing lipoproteins, as indicated by their positive staining with MB 47, a monoclonal antibody against apoB-100. A smooth muscle cell was observed to be in the process of phagocytosing one such exocytosed granule, and in the vicinity of a degranulated mast cell a foam cell contained an ingested mast cell granule. Therefore, the micrographs show that exocytosed granules of intimal mast cells may contribute to intimal foam cell formation and suggest a role for mast cells in human atherogenesis. More generally, the findings provide evidence that phagocytosis of apoB-100-carrying particles is one mechanism by which lipoproteins enter human arterial intimal cells.