Title | Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Haka AS, Barbosa-Lorenzi VC, Lee HJong, Falcone DJ, Hudis CA, Dannenberg AJ, Maxfield FR |
Journal | J Lipid Res |
Volume | 57 |
Issue | 6 |
Pagination | 980-92 |
Date Published | 2016 06 |
ISSN | 1539-7262 |
Keywords | Adipocytes, 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. |
DOI | 10.1194/jlr.M064089 |
Alternate Journal | J Lipid Res |
PubMed ID | 27044658 |
PubMed Central ID | PMC4878183 |
Grant List | R01 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.