Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation.

TitleExocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation.
Publication TypeJournal Article
Year of Publication2016
AuthorsHaka AS, Barbosa-Lorenzi VC, Lee HJong, Falcone DJ, Hudis CA, Dannenberg AJ, Maxfield FR
JournalJ Lipid Res
Volume57
Issue6
Pagination980-92
Date Published2016 06
ISSN1539-7262
KeywordsAdipocytes, Adipose Tissue, Animals, Exocytosis, Foam Cells, Humans, Lysosomes, Macrophages, Mice, Obesity, Phagocytosis
Abstract

Many types of apoptotic cells are phagocytosed and digested by macrophages. Adipocytes can be hundreds of times larger than macrophages, so they are too large to be digested by conventional phagocytic processes. The nature of the interaction between macrophages and apoptotic adipocytes has not been studied in detail. We describe a cellular process, termed exophagy, that is important for macrophage clearance of dead adipocytes and adipose tissue homeostasis. Using mouse models of obesity, human tissue, and a cell culture model, we show that macrophages form hydrolytic extracellular compartments at points of contact with dead adipocytes using local actin polymerization. These compartments are acidic and contain lysosomal enzymes delivered by exocytosis. Uptake and complete degradation of adipocyte fragments, which are released by extracellular hydrolysis, leads to macrophage foam cell formation. Exophagy-mediated foam cell formation is a highly efficient means by which macrophages internalize large amounts of lipid, which may ultimately overwhelm the metabolic capacity of the macrophage. This process provides a mechanism for degradation of objects, such as dead adipocytes, that are too large to be phagocytosed by macrophages.

DOI10.1194/jlr.M064089
Alternate JournalJ Lipid Res
PubMed ID27044658
PubMed Central IDPMC4878183
Grant ListR01 HL093331 / HL / NHLBI NIH HHS / United States
S10 RR029300 / RR / NCRR NIH HHS / United States
S10 RR017291 / RR / NCRR NIH HHS / United States
R00 HL092234 / HL / NHLBI NIH HHS / United States
S10 OD019994 / OD / NIH HHS / United States
R01 CA154481 / CA / NCI NIH HHS / United States
R37 DK027083 / DK / NIDDK NIH HHS / United States
C06 RR017528 / RR / NCRR NIH HHS / United States
K99 HL092234 / HL / NHLBI NIH HHS / United States
Related Faculty: 
Domenick J. Falcone, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700