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Leukocyte lipid bodies — Biogenesis and functions in inflammation
Authors:Patricia T Bozza  Kelly G Magalhães  Peter F Weller
Institution:1. Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil;2. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Abstract:Lipid body accumulation within leukocytes is a common feature in both clinical and experimental infectious, neoplasic and other inflammatory conditions. Here, we will review the contemporary evidence related to the biogenesis and structure of leukocyte lipid bodies (also known as lipid droplets) as inflammatory organelles. Studies of leukocyte lipid bodies are providing functional, ultrastructural and protein compositional evidences that lipid bodies are not solely storage depots of neutral lipid. Over the past years substantial progresses have been made to demonstrate that lipid body biogenesis is a highly regulated process, that culminate in the compartmentalization of a specific set of proteins and lipids, that place leukocyte lipid bodies as inducible cytoplasmic organelles with roles in cell signaling and activation, regulation of lipid metabolism, membrane trafficking and control of the synthesis and secretion of inflammatory mediators. Pertinent to the roles of lipid bodies in inflammation and cell signaling, enzymes involved in eicosanoid synthesis are localized at lipid bodies and lipid bodies are sites for eicosanoid generation. Collectively, lipid bodies in leukocytes are emerging as critical regulators of different inflammatory diseases, key markers of leukocyte activation and attractive targets for novel anti-inflammatory therapies.
Keywords:5-LO  5-lipoxygenase  AA  arachidonic acid  ACAT  acyl-coenzyme A:cholesterol acyltransferase  ADRP  adipose differentiation related protein  BCG  Bacillus Calmett Guerrin  COX  cyclooxygenase  cPLA2  cytosolic phospholipase A2  EDAC  1-ethyl-3 (3-dimethylamino-propyl) carbodiimide  ER  endoplasmic reticulum  EM  electron microscopy  FLAP  5-lipoxygenase activating protein  IL  interleukin  LDL  low density lipoprotein  LPS  lipopolysaccharide  LT  leukotriene  MAP  mitogen-activated protein  MCP-1  monocyte chemotactic protein-1  NSAID  non-steroidal anti-inflammatory drug  PI3K  phosphatidylinositide 3 kinase  PG  prostaglandin  PKC  protein kinase C  PPAR  Peroxisome Proliferator-Activated Receptor  TIP 47  tail-interacting protein of 47   kDa  TLR  toll-like receptor
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