Regulation of CXCL12 and CXCR4 expression by human brain endothelial cells and their role in CD4+ and CD8+ T cell adhesion and transendothelial migration

The basis for T cell adhesion to airway epithelial and vascular endothelial cells was studied using a quantitative flow cytometry-based assay that avoids extensive leukocyte purification and labeling. Compared with standard cell-labeling methods, the flow cytometry-based assay yielded a lower level of constitutive T cell adhesion, despite a similar level of stimulated adhesion (after T cell activation with phorbol dibutyrate) using endothelial or epithelial cell monolayers. Endothelial T cell adhesion was further increased by monolayer treatment with tumor necrosis factor-alpha (less so with interleukin-1 beta and least with interferon-gamma), whereas epithelial T cell adhesion was most sensitive to interferon-gamma. Cytokine stimulation of adhesion was invariably concentration dependent and closely matched to the cellular levels of intracellular adhesion molecule-1 (ICAM-1). Accordingly, stimulated T cell adhesion was markedly inhibited by anti-ICAM-1 or anti-beta 2-integrin antibody (95-97% inhibition for epithelial cells and 57-67% inhibition for endothelial cells) directed against ICAM-1 interaction with lymphocyte function-associated antigen-1 (LFA-1; alpha L beta 2-integrin). Residual endothelial T cell adhesion that correlated with endothelial vascular cell adhesion molecule-1 (VCAM-1) levels was blocked by an anti-alpha 4-integrin antibody directed against VCAM-1 interaction with very late activation antigen-4 (VLA-4; alpha 4 beta 1-integrin). The results suggest that 1) peripheral blood T cells without exogenous activation exhibit little LFA-1- or VLA-4-dependent adherence except to endothelial or epithelial cells expressing high levels of ICAM-1 and/or VCAM-1; and 2) differences in endothelial vs. epithelial cell mechanisms to bind activated and unactivated T cells (e.g., dependence on a mixed- vs. a single-ligand system and distinct cytokine-responsiveness of ligand levels) may help to coordinate T cell traffic to epithelial barriers.

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β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1

AJP Cell Physiology ◽

10.1152/ajpcell.2000.279.6.c1772 ◽

2000 ◽

Vol 279 (6) ◽

pp. C1772-C1781 ◽

Cited By ~ 130

Author(s):

Ranjit Giri ◽

Yamin Shen ◽

Monique Stins ◽

Shi Du Yan ◽

Ann Marie Schmidt ◽

...

Keyword(s):

Endothelial Cells ◽

Human Brain ◽

Cerebrovascular Disorders ◽

Amyloid Β ◽

Transendothelial Migration ◽

Peripheral Circulation ◽

Amyloid Peptide ◽

Brain Endothelial Cells ◽

Blood Monocytes ◽

The Brain

In patients with amyloid β-related cerebrovascular disorders, e.g., Alzheimer's disease, one finds increased deposition of amyloid peptide (Aβ) and increased presence of monocyte/microglia cells in the brain. However, relatively little is known of the role of Aβ in the trafficking of monocytes across the blood-brain barrier (BBB). Our studies show that interaction of Aβ1–40 with monolayer of human brain endothelial cells results in augmented adhesion and transendothelial migration of monocytic cells (THP-1 and HL-60) and peripheral blood monocytes. The Aβ-mediated migration of monocytes was inhibited by antibody to Aβ receptor (RAGE) and platelet endothelial cell adhesion molecule (PECAM-1). Additionally, Aβ-induced transendothelial migration of monocytes were inhibited by protein kinase C inhibitor and augmented by phosphatase inhibitor. We conclude that interaction of Aβ with RAGE expressed on brain endothelial cells initiates cellular signaling leading to the transendothelial migration of monocytes. We suggest that increased diapedesis of monocytes across the BBB in response to Aβ present either in the peripheral circulation or in the brain parenchyma may play a role in the pathophysiology of Aβ-related vascular disorder.

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Prostaglandin E1 inhibits TNFalpha-induced T-cell adhesion to endothelial cells by selective down-modulation of ICAM-1 expression on endothelial cells*

Experimental Dermatology ◽

10.1111/j.1600-0625.1995.tb00209.x ◽

1995 ◽

Vol 4 (5) ◽

pp. 302-307 ◽

Cited By ~ 15

Author(s):

J. M. Weiss ◽

K. A. Pilarski ◽

A. Wcyl ◽

M. Peschen ◽

E. Schopf ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Adhesion ◽

T Cell ◽

Prostaglandin E1 ◽

T Cell Adhesion

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Salicylates Inhibit Adhesion and Transmigration of T Lymphocytes by Preventing Integrin Activation Induced by Contact With Endothelial Cells

Blood ◽

10.1182/blood.v92.7.2389.2389_2389_2398 ◽

1998 ◽

Vol 92 (7) ◽

pp. 2389-2398 ◽

Cited By ~ 1

Author(s):

Roberto Gerli ◽

Cristina Paolucci ◽

Paolo Gresele ◽

Onelia Bistoni ◽

Stefano Fiorucci ◽

...

Keyword(s):

T Cells ◽

Endothelial Cells ◽

Cell Adhesion ◽

T Cell ◽

T Lymphocytes ◽

Cell Function ◽

Static System ◽

Functional Changes ◽

And Migration ◽

T Cell Adhesion

The inhibition of cyclooxygenase does not fully account for the spectrum of activities of nonsteroidal antiinflammatory drugs. It is evident, indeed, that regulation of inflammatory cell function may contribute in explaining some of the effects of these drugs. Tissue recruitment of T cells plays a key role in the development of chronic inflammation. Therefore, the effects of salicylates on T-cell adhesion to and migration through endothelial cell monolayers on collagen were analyzed in an in vitro static system. Aspirin and sodium salicylate reduced the ability of unstimulated T cells to adhere to and transmigrate through cytokine-activated endothelium. Although salicylates did not modify the expression of integrins on T cells, they blunted the increased adherence induced by the anti-β2monoclonal antibody (MoAb) KIM127 and prevented the appearance of an activation-dependent epitope of the CD11/CD18 complex, recognized by the MoAb 24, induced by contact with endothelial cells. Salicylates also induced an increase of intracellular calcium ([Ca2+]i) and activation of protein kinase C (PKC) in T cells, but not cell proliferation and interleukin (IL)-2 synthesis. The reduction of T-cell adhesiveness appears to be dependent on the increase in[Ca2+]i levels, as it could be reversed by blocking Ca2+ influx, but not by inhibiting PKC. Moreover, ionomycin at concentrations giving an increase in [Ca2+]i similar to that triggered by aspirin, strictly reproduced the T-cell phenotypic and functional changes induced by salicylates. Aspirin reduced T-cell adhesion and migration also ex vivo after infusion to healthy volunteers. These data suggest that the antiinflammatory activity of salicylates may be due, at least in part, to an interference with the integrin-mediated binding of resting T lymphocytes to activated endothelium with consequent reduction of a specific T-cell recruitment into inflammatory sites.

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