Lipid bodies are ill-understood, lipid-rich cytoplasmic organelles characteristically more abundant in vivo in leukocytes and other cells associated with inflammatory reactions. Ongoing investigations of the formation and function of these enigmatic intracellular structures demonstrate that lipid bodies have distinct functional roles as specialized, inducible organelles active in inflammatory responses of leukocytes and other cells. Lipid bodies are sites of enhanced eicosanoid formation that function as both intracrine/autocrine and paracrine mediators of inflammatory responses. Therefore, of pertinence to cells involved in inflammation, lipid bodies are distinct intracellular organelles whose formation within cells is rapidly and specifically inducible making them """"""""early response"""""""" structures, active as discrete intracellular loci involved in the regulated formation of eicosanoids. The investigations will use a combination of biochemical, ultrastructural, cytochemical, molecular biological and proteomic approaches to study lipid bodies in leukocytes and other cell types, both in situ within cells and as isolated subcellular structures. The goals will be to: 1) study the regulated formation and function of eicosanoids within lipid bodies, and 2) study the biogenesis and formation of lipid body organelles in leukocytes. The planned investigations will define the roles of lipid bodies as dynamic, inducible intracellular organelles active in the regulated metabolism of arachidonic acid and in other acute inflammatory responses of cells. Understanding the functions of lipid bodies will help elucidate mechanisms responsible for the heightened formation of biologically-active eicosanoid mediators, especially those involved in inflammatory reactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI022571-16A1
Application #
6547989
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Voulgaropoulou, Frosso
Project Start
1985-07-01
Project End
2007-06-30
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
16
Fiscal Year
2002
Total Cost
$382,500
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Melo, Rossana C N; Weller, Peter F (2018) Contemporary understanding of the secretory granules in human eosinophils. J Leukoc Biol 104:85-93
Weller, Peter F; Spencer, Lisa A (2017) Functions of tissue-resident eosinophils. Nat Rev Immunol 17:746-760
Melo, Rossana C N; Weller, Peter F (2016) Lipid droplets in leukocytes: Organelles linked to inflammatory responses. Exp Cell Res 340:193-7
Melo, Rossana C N; Weller, Peter F (2016) Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy. Exp Cell Res 347:385-90
Weller, Peter F (2016) LEUKOCYTE LIPID BODIES - STRUCTURE AND FUNCTION AS ""EICOSASOMES"". Trans Am Clin Climatol Assoc 127:328-340
Akuthota, Praveen; Carmo, Lívia A S; Bonjour, Kennedy et al. (2016) Extracellular Microvesicle Production by Human Eosinophils Activated by ""Inflammatory"" Stimuli. Front Cell Dev Biol 4:117
Carmo, Lívia A S; Dias, Felipe F; Malta, Kássia K et al. (2015) Expression and subcellular localization of the Qa-SNARE syntaxin17 in human eosinophils. Exp Cell Res 337:129-135
Melo, Rossana C N; Weller, Peter F (2014) Unraveling the complexity of lipid body organelles in human eosinophils. J Leukoc Biol 96:703-12
Dias, Felipe F; Amaral, Kátia B; Carmo, Lívia A S et al. (2014) Human Eosinophil Leukocytes Express Protein Disulfide Isomerase in Secretory Granules and Vesicles: Ultrastructural Studies. J Histochem Cytochem 62:450-459
Kovalszki, Anna; Weller, Peter F (2014) Eosinophilia in mast cell disease. Immunol Allergy Clin North Am 34:357-64

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