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Engineered Nanostructures of Haptens Lead to Unexpected Formation of Membrane Nanotubes Connecting Rat Basophilic Leukemia Cells

Journal Article · · ACS Nano
 [1];  [1];  [1];  [1];  [1];  [2];  [2];  [3];  [1]
  1. Univ. of California, Davis, CA (United States). Dept. of Chemistry
  2. Univ. of California Davis, Sacramento, CA (United States). School of Medicine, Dept. of Dermatology; Academia Sinica, Taipei (Taiwan). Inst. of Biomedical Sciences
  3. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
We report here on a recent finding that co-stimulation of the high-affinity immunoglobulin E (IgE) receptor (FcεRI) and the chemokine receptor 1 (CCR1) triggered formation of membrane nanotubes among bone-marrow-derived mast cells. The co-stimulation was attained using corresponding ligands: IgE binding antigen and macrophage inflammatory protein 1α (MIP1 α), respectively. However, this approach failed to trigger formation of nanotubes among rat basophilic leukemia (RBL) cells due to the lack of CCR1 on the cell surface (Int. Immunol. 2010, 22 (2), 113–128). RBL cells are frequently used as a model for mast cells and are best known for antibody-mediated activation via FcεRI. This work reports the successful formation of membrane nanotubes among RBLs using only one stimulus, a hapten of 2,4-dinitrophenyl (DNP) molecules, which are presented as nanostructures with our designed spatial arrangements. This observation underlines the significance of the local presentation of ligands in the context of impacting the cellular signaling cascades. In the case of RBL, certain DNP nanostructures suppress antigen-induced degranulation and facilitate the rearrangement of the cytoskeleton to form nanotubes. We conclude that these results demonstrate an important scientific concept; engineered nanostructures enable cellular signaling cascades, where current technologies encounter great difficulties. More importantly, nanotechnology offers a new platform to selectively activate and/or inhibit desired cellular signaling cascades.
Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE National Nuclear Security Administration (NNSA)
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1282122
Alternate ID(s):
OSTI ID: 1809177
Report Number(s):
LLNL-JRNL--822115
Journal Information:
ACS Nano, Journal Name: ACS Nano Journal Issue: 7 Vol. 9; ISSN 1936-0851
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English

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