ATP increases the migration of microglia across the brain endothelial cell monolayer
نویسندگان
چکیده
The cerebral microcapillary endothelium, known as the blood-brain barrier (BBB), acts as a barrier between the blood and the interstitial fluid of the brain. The BBB therefore controls the passage of nutrients into the central nervous system (CNS). Microglia show a specific affinity for migration into the CNS, and this migration appears to occur independently of BBB integrity. To study the migration of microglia across the BBB, we developed an in vitro co-culture system of mouse brain endothelial cells (MBECs) and Ra2 microglia using Transwell inserts. We first investigated the influence of microglia or ATP, a microglial chemotactic factor, on MBEC barrier integrity. The addition of microglia or ATP led to the disruption of the MBEC monolayer and significantly decreased barrier function as measured by trans-endothelial electrical resistance (TEER) and electric cell-substrate impedance sensing (ECIS). Furthermore, ATP promoted the migration of microglia but not macrophages across the MBEC monolayer. An inhibitor of matrix metalloproteinases (MMPs) decreased the transmigration of microglia in our system, indicating that MMPs play a role in microglial chemotaxis. We specifically identify a role for microglia-derived MMP-2. In conclusion, we offer evidence that microglia migration across the brain endothelial cell monolayer is increased in the presence of ATP in a manner that involves MMP secretion.
منابع مشابه
تمایز سلولهای دندریتیک مشتق از مونوسیت بر روی لایهای از سلولهای اندوتلیال بهعنوان لایه تغذیهکننده
Background: The innate and adaptive immune responses are dependent on the migration of leukocytes across endothelial cells. Dendritic cells (DCs) play an important role in the initiation of cellular immune responses during their migration from tissues into the lymph nodes where they interact with endothelial cells of lymphatic vessels. We investigated the effect...
متن کاملEffect of endothelial cell polarity on beta-amyloid-induced migration of monocytes across normal and AD endothelium.
During normal aging and amyloid beta-peptide (Abeta) disorders such as Alzheimer's disease (AD), one finds increased deposition of Abeta and activated monocytes/microglial cells in the brain. Our previous studies show that Abeta interaction with a monolayer of normal human brain microvascular endothelial cells results in increased adherence and transmigration of monocytes. Relatively little is ...
متن کاملO 7: KCNK2 Regulates the Nanoscale Formation of Immune Docking Structures on Brain Endothelial Cells Under Autoinflammatory Conditions
KCNK2 was previously shown to regulate immune-cell trafficking into the central nervous system (CNS). Kcnk2-/- mice demonstrated a more severe disease course in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, due to an increased immune-cell migration into the CNS. An upregulation of the cellular adhesion molecules ICAM1 and VCAM1 on brain endothelial cells in K...
متن کاملMicroglia as a stem cell
Microglia is considered the only cell population of mesodermal origin, which comprises 10% of the cells in brain parenchyma. Recent neural stem cell (NSC) studies demonstrate that the brain has regenerative potential. NSCs do not give rise to microglial cells, however indicating that NSCs alone cannot complete the regenetion of the brain. Although the role of microglia is not fully understood, ...
متن کاملP 89: Reduction of Neuroinflammation in Epilepsy by Using Stem Cells Derived Astrocytes
Epilepsy is neurological disorders that afflict many people around the world with a higher prevalence rate in children and in low income countries. Temporal lobe epilepsy (TLE) is result from hippocampal sclerosis is a neurological disorder with difficult treatment. Stem cells can transform into any type of cells such as glial cells, consequently stem cells can use for medical treatment. Stem c...
متن کامل