Lipid bodies are cytoplasmic inclusions that develop in leukocytes, including eosinophils and mast cells, associated with allergic inflammation. Our investigations of the formation and function of leukocyte lipid bodies have revealed that they are distinct, inducible endoplasmic reticulum (ER)-derived, membrane- and ribosome-containing organelles with diverse functional roles in inflammatory responses of leukocytes pertinent to allergic inflammation. Leukocyte lipid bodies contain all enzymes required for synthesizing cyclooxygenase (COX)- and lipoxygenase (LO)-derived eicosanoids. Lipid body formation, rapidly inducible in vitro and in vivo by specific intracellular signaling pathways, enhances leukocyte formation of COX- and LO-derived eicosanoids. Lipid bodies are discrete sites of new eicosanoid synthesis, as documented for immunolocalized LTC4, LTB4 and PGE2. Lipid body-derived eicosanoids function as both paracrine and intracrine mediators of allergic inflammation. Based on combined proteomic and ultrastructural studies, leukocyte lipid bodies are complex organelles with internal membranes and ribosomes whose proteome includes proteins involved in protein synthesis. In IgE-activated cells, lipid bodies are early sites of agonist- elicited 5-LO mRNA localization and de novo 5-LO, LTC4 synthase and cytosolic phospholipase A2 protein synthesis. In addition, lipid bodies are sites of localization of cytokines, including TNF- demonstrable in vivo in tissue and blood leukocytes, although mechanisms and consequences of lipid body cytokine local- ization are unknown. Our central hypothesis is that leukocyte lipid bodies associated with allergic inflammation are inducible organelles that have major roles in the regulated formation of eicosanoids and cytokines that function as intra- and extracellular mediators of allergic inflammation. Our investigations have three aims: 1) Investigate the formation and function of eicosanoids within lipid bodies by evaluating the regulation of eicosanoid- synthesizing enzymes at lipid bodies, including 5-LO regulatory interactions with other proteins in lipid bodies and lipid bodies as sites of differential eicosanoid formation. 2) Investigate the formation and function of cytokines within lipid bodies by studying mechanisms regulating the formation and accumulation of cytokines within leukocyte lipid bodies and whether lipid body localized cytokines function locally within lipid bodies by signaling via cytokine receptors present within lipid bodies. 3) Investigate the mechanisms regulating leukocyte lipid body-related mRNA expression and function. The planned studies aim to provide a better understanding of mechanisms by which leukocytes contribute to inflammation pertinent to allergic and other diseases.

Public Health Relevance

Asthma and related disorders due to allergic inflammation are increasingly prevalent diseases. The research will help in understanding mechanisms of allergic inflammation that are responsible for making asthma and allergic diseases major public health problems.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section (HAI)
Program Officer
Minnicozzi, Michael
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Beth Israel Deaconess Medical Center
United States
Zip Code
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
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
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
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

Showing the most recent 10 out of 91 publications