Immunobiology of the blood-brain barrier

Miller, Donald W.

doi:10.3109/13550289909021286

Cited by 98 publications

(66 citation statements)

References 58 publications

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“…In vivo, the BBB is a dynamic and integrated structure in which brain endothelial cells are intimately associated with other cell types, including pericytes, perivascular macrophages, and astrocytic foot processes (54). In prior work, we found that the addition of astrocyte-conditioned medium to HBECs decreased the permeability of soluble molecules across this barrier, but did not affect cellular migration (55).…”

Section: Discussionmentioning

confidence: 99%

Determinants of Human B Cell Migration Across Brain Endothelial Cells

Alter

Duddy

Hebert

et al. 2003

The Journal of Immunology

174

123

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Circulating B cells enter the CNS as part of normal immune surveillance and in pathologic states, including the common and disabling illness multiple sclerosis. However, little is known about the molecular mechanisms that mediate human B cell interaction with the specialized brain endothelial cells comprising the blood-brain barrier (BBB). We studied the molecular mechanisms that regulate the migration of normal human B cells purified ex vivo, across human adult brain-derived endothelial cells (HBECs). We found that B cells migrated across HBECs more efficiently than T cells from the same individuals. B cell migration was significantly inhibited by blocking Abs to the adhesion molecules ICAM-1 and VLA-4, but not VCAM-1, similar to the results previously reported for T cells. Blockade of the chemokines monocyte chemoattractant protein-1 and IL-8, but not RANTES or IFN-γ-inducible protein-10, significantly inhibited B cell migration, and these results were correlated with the chemokine receptor expression of B cells measured by flow cytometry and by RNase protection assay. Tissue inhibitor of metalloproteinase-1, a natural inhibitor of matrix metalloproteinases, significantly decreased B cell migration across the HBECs. A comprehensive RT-PCR comparative analysis of all known matrix metalloproteinases and tissue inhibitors of metalloproteinases in human B and T cells revealed distinct profiles of expression of these molecules in the different cell subsets. Our results provide insights into the molecular mechanisms that underlie human B cell migration across the BBB. Furthermore, they identify potential common, and unique, therapeutic targets for limiting CNS B cell infiltration and predict how therapies currently developed to target T cell migration, such as anti-VLA-4 Abs, may impact on B cell trafficking.

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Section: Discussionmentioning

confidence: 99%

Determinants of Human B Cell Migration Across Brain Endothelial Cells

Alter

Duddy

Hebert

et al. 2003

The Journal of Immunology

174

123

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“…In addition, the endothelium serves as a selective permeability barrier between the blood and tissue, including the brain (Albert et al 1997), and produces a variety of growth factors and peptide hormones ( Miller 1999, Vapaatalo & Mervaala 2001. While multiple signaling pathways impact on these diverse end points, many of these diverse cell functions including nitric oxide (NO) production by endothelial NO synthase (eNOS) and prostanoid production in response to cytosolic phospholipase A2 activation are thought to be mediated by Ca 2C signaling.…”

Section: Introductionmentioning

confidence: 99%

Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction

Gifford¹,

Feng²,

Bird³

2006

Journal of Endocrinology

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We have previously shown that endothelial cells (EC) derived from the uterine artery (UA) of both pregnant (P-UAEC) and nonpregnant (NP-UAEC) ewes show a biphasic intracellular free Ca 2C ([Ca 2C ] i ) response after ATP stimulation. In each case, the initial transient peak, caused by the release of Ca 2C from the intracellular Ca 2C stores, is mediated by purinergic receptor-Y2 and is very similar in both cell types. However, the sustained phase in particular, caused by the influx of extracellular Ca 2C, is heightened in the P-UAEC, and associates with an increased ability of the cells to demonstrate enhanced capacitative Ca 2C entry (CCE) via store-operated channels (SOCs). Herein we demonstrated that the difference in the sustained [Ca 2C ] i response is maintained for at least 30 min. When 2-aminoethoxydiphenyl borate (2APB) (an inhibitor of the inosital 1,4,5-trisphosphate receptor (IP3R) and possibly SOC) was used in conjunction with ATP, it was capable of completely inhibiting CCE. Since 2APB can inhibit SOC in some cell types and 2APB was capable of inhibiting CCE in the UAEC model, the role of SOC in CCE was first evaluated using the classical inhibitor La ] i response. Since canonical transient receptor potential channels (TRPCs) have recently been identified as putative SOCs in many cell types, including EC, the expression levels of several isoforms were evaluated in UAEC. Expression of TRPC3 and TRPC6 channels in particular was detected, but no significant difference in expression level was found between NP-and P-UAEC. Nonetheless, we were able to show that IP3R2 interacts with TRPC3 in UAEC, forming a protein complex, and that this interaction is considerably enhanced in an agonist sensitive manner by pregnancy. Thus, while IP3R and TRPC isoforms are not altered in their expression by pregnancy, enhanced functional interaction of TRPC3 with IP3R2 may underlie pregnancy-enhanced CCE in the UAEC model and so explain the prolonged [Ca 2C ] i sustained phase seen in response to ATP.

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“…Brain endothelial cells and immune cells activated by cytokines or infection overexpress adhesion molecules and their ligands, promoting the binding of circulating immune cells to brain vasculature (36). Such binding could be the first step in diapedesis, the passage of immune cells across the BBB (44). This close proximity could also facilitate the passage of virus between the infected immune cell and the brain endothelial cell, analogous to the transfer of virus between infected immune cells and epithelial cells (14).…”

mentioning

confidence: 99%

Transport of Human Immunodeficiency Virus Type 1 Pseudoviruses across the Blood-Brain Barrier: Role of Envelope Proteins and Adsorptive Endocytosis

Banks

Freed

Wolf

et al. 2001

J Virol

125

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Blood-borne human immunodeficiency virus type 1 (HIV-1) crosses the blood-brain barrier (BBB) to induce brain dysfunction. How HIV-1 crosses the BBB is unclear. Most work has focused on the ability of infected immune cells to cross the BBB, with less attention devoted to the study of free virus. Since the HIV-1 coat glycoprotein gp120 can cross the BBB, we postulated that gp120 might be key in determining whether free virus can cross the BBB. We used radioactive virions which do (Env ؉ ) or do not (Env ؊ ) bear the envelope proteins to characterize the ability of HIV-1 to be taken up by the murine BBB. In vivo and in vitro studies showed that the envelope proteins are key to the uptake of free virus and that uptake was enhanced by wheat germ agglutinin, strongly suggesting that the envelope proteins induce viral adsorptive endocytosis and transcytosis in brain endothelia. Capillary depletion showed that Env ؉ virus completely crossed the vascular BBB to enter the parenchyma of the brain. Virus also entered the cerebrospinal fluid, suggesting passage across the choroid plexus as well. About 0.22% of the intravenously injected dose was taken up per g of brain. In vitro studies showed that postinternalization membrane cohesion (membrane binding not reversed with acid wash or cell lysis) was a regulated event. Intact virus was recovered from the brain endothelial cytosol and was effluxed from the endothelial cells. These results show that free HIV-1 can cross the BBB by an event related to adsorptive endocytosis and mediated by the envelope proteins.

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Immunobiology of the blood-brain barrier

Cited by 98 publications

References 58 publications

Determinants of Human B Cell Migration Across Brain Endothelial Cells

Determinants of Human B Cell Migration Across Brain Endothelial Cells

Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction

Transport of Human Immunodeficiency Virus Type 1 Pseudoviruses across the Blood-Brain Barrier: Role of Envelope Proteins and Adsorptive Endocytosis

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