The Internal Architecture of Leukocyte Lipid Body Organelles Captured by Three-Dimensional Electron Microscopy Tomography
Melo, Rossana C. N.
Paganoti, Guillherme F.
MetadataShow full item record
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.
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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11181172
- HMS Scholarly Articles 
Contact administrator regarding this item (to report mistakes or request changes)
Showing items related by title, author, creator and subject.
The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection Ali, Youssif M.; Lynch, Nicholas J.; Haleem, Kashif S.; Fujita, Teizo; Endo, Yuichi; Hansen, Soren; Holmskov, Uffe; Takahashi, Kazue; Stahl, Gregory L.; Dudler, Thomas; Girija, Umakhanth V.; Wallis, Russell; Kadioglu, Aras; Stover, Cordula M.; Andrew, Peter W.; Schwaeble, Wilhelm J. (Public Library of Science, 2012)The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information ...
R5-SHIV Induces Multiple Defects in T Cell Function during Early Infection of Rhesus Macaques Including Accumulation of T Reg Cells in Lymph Nodes Righi, Elda; Leblanc, Pierre R.; Kodish, Brett; Mylvaganam, Hari N.; Stevceva, Liljana; Hu, Shiu-Lok; Chenine, Agnes-L.; Hovav, Avi-Hai; Unutmaz, Derya; Santosuosso, Michael Robert; Siddappa, Nagadenahalli B.; Ghebremichael, Musie Syum; Ruprecht, Ruth Margrit; Poznansky, Mark; Hill, David E. (Public Library of Science, 2011)Background: HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune ...
TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection Jayaraman, Pushpa; Jacques, Miye K.; Zhu, Chen; Steblenko, Katherine M.; Stowell, Britni L.; Madi, Asaf; Anderson, Ana C.; Kuchroo, Vijay K.; Behar, Samuel M. (Public Library of Science, 2016)While T cell immunity initially limits Mycobacterium tuberculosis infection, why T cell immunity fails to sterilize the infection and allows recrudescence is not clear. One hypothesis is that T cell exhaustion impairs ...