Blood-Brain Barrier and Immune Cell Transmigration: Pathways Overview
Click on one of the molecules below to see the signaling pathway activated by that molecule and the changes it induces in the integrity of the blood-brain barrier.
Get Print CopyRedistribution of TJ and AJ Proteins
Redistribution of TJ and AJ Proteins
MMP Expression and TJ Protein Degradation
MMP Expression and TJ Protein Degradation
Stress Fiber Formation
Stress Fiber Formation
alpha4 beta1
(VLA-4)
alpha4 beta1
(VLA-4)
alpha L beta 2
(LFA-1)
alpha L beta 2
(LFA-1)
Redistribution of TJ and AJ Proteins
Redistribution of TJ and AJ Proteins
Stress Fiber Formation
Stress Fiber Formation
Loss of Pericytes
Loss of Pericytes
Migration
Migration
Cleavage
Cleavage
ECM Degradation
ECM Degradation
Chemotaxis
Chemotaxis
ECM Degradation
ECM Degradation
CCL2/MCP-1
CCL2/MCP-1
TNF-alpha
VEGF
CCL2/MCP-1
TNF-alpha
VEGF
CCL2/MCP-1
TNF-alpha
CCL2/MCP-1
TNF-alpha
CCL2/MCP-1
MMP-9
MMP-9
ECM Degradation
ECM Degradation
Chemotaxis
Chemotaxis
CCL2/MCP-1
CCL3/MIP-1 alpha
CCL2/MCP-1
CCL3/MIP-1 alpha
Expression
Expression
Overview of Blood-Brain Barrier and Immune Cell Transmigration: Overview
The blood-brain barrier (BBB) is a highly specialized, multi-cellular structure that functions as a selective diffusion barrier between the peripheral circulation and the central nervous system (CNS). The BBB is composed of specialized endothelial cells (ECs) that are linked by complex tight junctions (TJs) and adherens junctions (AJs). These cells are also surrounded by astrocytes and pericytes. Under normal conditions, the specialized structure of the BBB hinders paracellular transport of most hydrophilic compounds across the cerebral endothelium and restricts migration of blood-borne cells into the CNS. As a result, microglia, the resident immune cells of the CNS, are the initial responders to pathogens or tissue damage. However, prolonged tissue insult triggers inflammatory conditions that cause the BBB to lose its restrictive features, resulting in the subsequent infiltration of peripheral immune cells.
Reactive microglia, astrocytes, and pericytes, as well as ECs, release numerous molecules that promote invasion of peripheral immune cells into the CNS. Secreted inflammatory mediators, including CXCL8/IL-8, CCL2/MCP-1, TNF-alpha, IL-1beta/IL-1F2, recruit immune cells and stimulate the expression of adhesion molecules on ECs that participate in integrin-mediated leukocyte tethering, rolling, and activation. These pro-inflammatory molecules also trigger the dynamic reorganization of junction complexes between ECs, thereby promoting the formation of paracellular gaps. Matrix metalloproteases (MMPs), which are also released, degrade proteins present in the extracellular matrix (ECM) and may contribute to the loss of pericytes. These events lead to an increase in the permeability of the BBB and invasion of peripheral immune cells.
To learn more, please visit our Neuroinflammation Research Area.
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