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dc.contributor.authorMelo, Rossana C. N.
dc.contributor.authorPaganoti, Guillherme F.
dc.contributor.authorDvorak, Ann Marie
dc.contributor.authorWeller, Peter Fahey
dc.date.accessioned2013-10-18T14:01:46Z
dc.date.issued2013
dc.identifier.citationMelo, Rossana C. N., Guillherme F. Paganoti, Ann M. Dvorak, and Peter F. Weller. 2013. The internal architecture of leukocyte lipid body organelles captured by three-dimensional electron microscopy tomography. PLoS ONE 8(3): e59578.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11181172
dc.description.abstractLipid bodies (LBs), also known as lipid droplets, are complex organelles of all eukaryotic cells linked to a variety of biological functions as well as to the development of human diseases. In cells from the immune system, such as eosinophils, neutrophils and macrophages, LBs are rapidly formed in the cytoplasm in response to inflammatory and infectious diseases and are sites of synthesis of eicosanoid lipid mediators. However, little is known about the structural organization of these organelles. It is unclear whether leukocyte LBs contain a hydrophobic core of neutral lipids as found in lipid droplets from adipocytes and how diverse proteins, including enzymes involved in eicosanoid formation, incorporate into LBs. Here, leukocyte LB ultrastructure was studied in detail by conventional transmission electron microscopy (TEM), immunogold EM and electron tomography. By careful analysis of the two-dimensional ultrastructure of LBs from human blood eosinophils under different conditions, we identified membranous structures within LBs in both resting and activated cells. Cyclooxygenase, a membrane inserted protein that catalyzes the first step in prostaglandin synthesis, was localized throughout the internum of LBs. We used fully automated dual-axis electron tomography to study the three-dimensional architecture of LBs in high resolution. By tracking 4 nm-thick serial digital sections we found that leukocyte LBs enclose an intricate system of membranes within their “cores”. After computational reconstruction, we showed that these membranes are organized as a network of tubules which resemble the endoplasmic reticulum (ER). Our findings explain how membrane-bound proteins interact and are spatially arranged within LB “cores” and support a model for LB formation by incorporating cytoplasmic membranes of the ER, instead of the conventional view that LBs emerge from the ER leaflets. This is important to understand the functional capabilities of leukocyte LBs in health and during diverse diseases in which these organelles are functionally involved.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0059578en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608657/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectImmunologyen_US
dc.subjectImmune Systemen_US
dc.subjectCytokinesen_US
dc.subjectImmunityen_US
dc.subjectImmune Activationen_US
dc.subjectInflammationen_US
dc.subjectInnate Immunityen_US
dc.subjectImmune Responseen_US
dc.subjectImmunomodulationen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCellular Structuresen_US
dc.subjectSubcellular Organellesen_US
dc.subjectCellular Typesen_US
dc.subjectImmune Cellsen_US
dc.subjectMedicineen_US
dc.subjectHematologyen_US
dc.subjectWhite Cellsen_US
dc.titleThe Internal Architecture of Leukocyte Lipid Body Organelles Captured by Three-Dimensional Electron Microscopy Tomographyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorWeller, Peter Fahey
dc.date.available2013-10-18T14:01:46Z
dc.identifier.doi10.1371/journal.pone.0059578*
dash.contributor.affiliatedDvorak, Ann
dash.contributor.affiliatedWeller, Peter


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