T-Space at The University of Toronto Libraries >
School of Graduate Studies - Theses >
Please use this identifier to cite or link to this item:
|Title: ||ICAM-1 as a Novel Binding Partner for LPS to Mediate TLR4-Independent Cell Activation|
|Authors: ||Pabari, Reena|
|Advisor: ||Zhang, Haibo|
|Issue Date: ||22-Sep-2009|
|Abstract: ||Introduction: The mechanism of cell activation by LPS in the absence of surface Toll-like receptor 4 (TLR4) is unclear. We hypothesize that ICAM-1 binds LPS on the cell surface, mediating cell activation independent of TLR4.
Methods: The interaction between murine ICAM-1 and LPS was measured in a binding assay. Alveolar macrophages (AMs) isolated from TLR4 deficient mice were stimulated with LPS. Cell activation was measured by flow cytometry and cytokine production. The role of ICAM-1 in cell activation was determined by siRNA transfection.
Results: Murine ICAM-1 binds LPS. TLR4 deficient AMs respond to LPS stimulation by upregulation of LPS binding sites, ICAM-1 expression and cytokine release. Cell activation is attenuated by treatment with polymyxin B and ICAM-1 gene silencing.
Conclusions: ICAM-1 binds LPS and is important in TLR4-independent cell activation. Strategies devised to target ICAM-1 may have the potential to block the excessive inflammatory response seen in gram-negative sepsis.|
|Appears in Collections:||Master|
This item is licensed under a Creative Commons License
Items in T-Space are protected by copyright, with all rights reserved, unless otherwise indicated.