Metabolism of LDL in mast cells recovering from degranulation. Description of a novel intracellular pathway leading to proteolytic modification of the lipoprotein.
Rat serosal mast cells contain cytoplasmic secretory granules composed of a proteoglycan matrix in which histamine and neutral proteases are embedded. On stimulation, these granules are exocytosed, but some of them remain in the degranulation channels where on exposure to the extracellular fluid, they lose their histamine and a fraction of their proteoglycans. In vitro, such granule remnants efficiently bind low density lipoprotein (LDL) present in the incubation medium. After a lag period of about 10 minutes, the granule remnants, still within the channels and coated with LDL particles, are internalized by the parent mast cells. During subsequent recovery from degranulation, the apolipoprotein B of the intracellularly located remnant-bound LDL becomes efficiently (up to 70%) degraded by the proteolytic enzymes of the granule remnants. Since the granule remnants lack cholesteryl esterase activity, no LDL cholesterol is made available for cellular nutrition. Instead, selective proteolytic degradation of the bound LDL leads to formation of LDL particles enlarged by fusion on the granule remnant surface. In response to restimulation of the mast cells, about 50% of the fused LDL particles are exocytosed with the granule remnants. Of these, about one in five are expelled into the incubation medium. The granule remnants that again remain in the degranulation channels bind and internalize more LDL. This "round trip" of LDL in mast cells exposed to repeated stimulation constitutes a hitherto-unknown intracellular pathway for modification of LDL.
Kokkonen
J O
JO
Wihuri Research Institute, Helsinki, Finland.
Lindstedt
K A
KA
Kovanen
P T
PT
D000818:Animals; D015550:Cell Degranulation; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism; D005089:Exocytosis; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
D008077:Lipoproteins, LDL; D010450:Endopeptidases