Vascular endothelial cell Toll-like receptor pathways in sepsis

The endothelium forms a vast network that dynamically regulates vascular barrier function, coagulation pathways and vasomotor tone. Microvascular endothelial cells are uniquely situated to play key roles during infection and injury, owing to their widespread distribution throughout the body and thei...

Full description

Saved in:
Bibliographic Details
Published in:Innate Immunity 2015-11, Vol.21 (8), p.827-846
Main Authors: Khakpour, Samira, Wilhelmsen, Kevin, Hellman, Judith
Format: Article
Language:English
Subjects:
Blood Coagulation
Capillary Permeability
Endothelium, Vascular - immunology
Endothelium, Vascular - metabolism
Humans
Immunity, Innate - physiology
Sepsis - immunology
Sepsis - metabolism
Signal Transduction
Toll-Like Receptors - immunology
Toll-Like Receptors - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The endothelium forms a vast network that dynamically regulates vascular barrier function, coagulation pathways and vasomotor tone. Microvascular endothelial cells are uniquely situated to play key roles during infection and injury, owing to their widespread distribution throughout the body and their constant interaction with circulating blood. While not viewed as classical immune cells, endothelial cells express innate immune receptors, including the Toll-like receptors (TLRs), which activate intracellular inflammatory pathways mediated through NF-κB and the MAP kinases. TLR agonists, including LPS and bacterial lipopeptides, directly upregulate microvascular endothelial cell expression of inflammatory mediators. Intriguingly, TLR activation also modulates microvascular endothelial cell permeability and the expression of coagulation pathway intermediaries. Microvascular thrombi have been hypothesized to trap microorganisms thereby limiting the spread of infection. However, dysregulated activation of endothelial inflammatory pathways is also believed to lead to coagulopathy and increased vascular permeability, which together promote sepsis-induced organ failure. This article reviews vascular endothelial cell innate immune pathways mediated through the TLRs as they pertain to sepsis, highlighting links between TLRs and coagulation and permeability pathways, and their role in healthy and pathologic responses to infection and sepsis.
ISSN:1753-4259
1753-4267
DOI:10.1177/1753425915606525