Interactions between endothelial cells and HIV-1

Bussolino, Federico; Mitola, Stefania; Serini, Guido; Barillari, Giovanni; Ensoli, Barbara

doi:10.1016/s1357-2725(01)00024-3

Cited by 57 publications

(37 citation statements)

References 191 publications

(196 reference statements)

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“…These cells are a heterogeneous population with 3 distinct phenotypes: one reminiscent of activated vascular and lymphatic ECs, the second of macrophagic and dendritic cells, and the last with mixed markers of macrophage and ECs. 51 Figure 4 shows that CCL16-Cos induced KS chemotaxis in a dose-dependent manner. …”

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confidence: 97%

CCL16 activates an angiogenic program in vascular endothelial cells

Strasly¹

2004

Blood

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Besides regulating leukocyte trafficking in normal and injured tissues, several chemokines may positively or negatively regulate angiogenesis. Here we report that CCL16 activates an angiogenic program in vascular endothelial cells by activating CCR1. CCL16 induces dose-dependent random and directional migration of endothelial cells isolated from large vessels and liver capillaries without inducing their proliferation. It also promotes endothelial differentiation into capillary-like structures in an in vitro assay and is angiogenic in the chick chorionallantoic membrane. These angiogenic activities are neutralized by a specific antibody against CCL16. The direct angiogenic activity of CCL16 is further amplified by its ability to prime endothelium to a mitogen signal induced by vascular endothelial growth factor A and to raise their basal production of CXCL8 and CCL2, 2 other angiogenic chemokines. BX471 ( IntroductionChemokines are polypeptide molecules mainly involved in the control of leukocyte functions and trafficking through the activation of receptors belonging to the 7-transmembrane spanning, G-protein-coupled receptor family. Near the NH 2 end of the molecule, the presence of cysteine residues identifies 4 subfamilies. They are characterized by the presence of a unique C, or of 2 Cs separated by a single (CXC) or 3 amino acids (CXXXC) or adjacent (CC), and show largely overlapping biologic activities. 1 CCL16, also known as liver-expressed chemokine or NCC-4 or lymphocyte and monocyte chemoattractant or HCC-4, is a CC chemokine that specifically attracts lymphocytes, dendritic cells, and monocytes; increases their adhesive properties; and has myelosuppressive activity. [2][3][4][5][6] It is constitutively expressed in liver 3,7 and is increased by interleukin 10 (IL-10) in activated monocytes. 2 Interestingly, CCL16 is present in human plasma suggesting that it may be active outside hepatic tissue. 7 CCR1, CCR2, CCR5, and CCR8 are the functional receptors of this chemokine. 5,7 CCL16 released by engineered tumor cells elicits their rejection by a CD8 ϩ -and neutrophil-dependent mechanism and a rapid induction of a tumor-specific systemic immune response. This suggests that CCL16 improves recognition of poorly immunogenic cells by promoting a cross talk between T lymphocytes and antigenpresenting cells. 8 The histochemical analysis of these tumors showed expression of adhesion molecules by endothelial cells (ECs), without signs of vascular necrosis or inhibition of angiogenesis, in spite of the abundant neutrophil infiltrate that usually characterizes other models of tumor rejection promoted by cytokines, where vasculature is severely affected. [9][10][11][12][13] Chemokines play a role in embryo and adult vascular bed formation. 14,15 Besides an indirect mechanism involving angiogenic inducers released by activated leukocytes, 16,17 both CC and CXC chemokines may directly activate a proangiogenic [18][19][20][21][22][23][24][25][26][27][28] or an angiostatic 19,[29][30][31][32][33][34][35] program in ECs...

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confidence: 97%

CCL16 activates an angiogenic program in vascular endothelial cells

Strasly¹

2004

Blood

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“…HIV-1 may productively infect human primary ECs in vitro, even though this is strongly debated (9,10). In vivo studies, however, failed convincingly to demonstrate the presence of viral particles in vascular lesions, suggesting that the mechanism of HIV-1-induced endothelial dysfunction may therefore rely on indirect action of HIV-1 proteins rather than being a direct effect of the virus itself (11).…”

mentioning

confidence: 99%

HIV-1 matrix protein p17 promotes angiogenesis via chemokine receptors CXCR1 and CXCR2

Caccuri¹,

Giagulli²,

Bugatti³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

106

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Vascular diseases supported by aberrant angiogenesis have increased incidence in HIV-1-infected patients. Several data suggest that endothelium dysfunction relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. The HIV-1 matrix protein p17 is known to deregulate the biological activity of different immune cells. Recently, p17 was found to mimic IL-8 chemokine activity by binding to the IL-8 receptor CXCR1. Here we show that p17 binds with high affinity to CXCR2, a CXCR1-related receptor, and promotes the formation of capillary-like structures on human endothelial cells (ECs) by interacting with both CXCR1 and CXCR2 expressed on the EC surface. ERK signaling via Akt was defined as the pathway responsible for p17-induced tube formation. Ex vivo and in vivo experimental models confirmed the provasculogenic activity of p17, which was comparable to that induced by VEGF-A. The hypothesis of a major role for p17 in HIV-1-induced aberrant angiogenesis is enforced by the finding that p17 is detected, as a single protein, in blood vessels of HIV-1-patients and in particular in the nucleus of ECs. Localization of p17 in the nucleus of ECs was evidenced also in in vitro experiments, suggesting the internalization of exogenous p17 in ECs by mechanisms of receptormediated endocytosis. Recognizing p17 interaction with CXCR1 and CXCR2 as the key event in sustaining EC aberrant angiogenesis could help us to identify new treatment strategies in combating AIDSrelated vascular diseases. extracellular viral proteins | virokine | Akt-mediated ERK pathway | vasculogenic assays | surface plasmon resonance A ngiogenesis is a physiological process requiring growth of new blood vessels from preexisting vessels. This process involves coordinated endothelial cell (EC) proliferation, invasion, migration, and tube formation (1). When new vessels are required, proangiogenic factors are produced, whereas restoration of physiological conditions is achieved by producing inhibitors of angiogenesis and vessel stabilization factors. Breakdown of the tight regulated angiogenic balance leads to dysfunctional endothelium, abnormal angiogenesis, and vascular diseases.

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“…HIV-1 profoundly alters the features of EC. Certain EC, such as those lining liver sinusoids, HUVEC, bone marrow stromal EC, or HBMEC, may be variably permissive for HIV infection (22). Activation of EC appears to occur in HIV infection.…”

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confidence: 99%

HIV-1 Tat-Mediated Apoptosis in Human Brain Microvascular Endothelial Cells

Kim

Avraham

Koh

et al. 2003

The Journal of Immunology

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The integrity of the blood-brain barrier (BBB) is critical for normal brain function. Neuropathological abnormalities in AIDS patients have been associated with perivascular HIV-infected macrophages, gliosis, and abnormalities in the permeability of the BBB. The processes by which HIV causes these pathological conditions are not well understood. To characterize the mechanism by which HIV-1 Tat protein modulates human brain microvascular endothelial cell (HBMEC) functions, we studied the effects of HIV-1 Tat in modulating HBMEC apoptosis and permeability. Treatment of HBMEC with HIV-1 Tat led to Flk-1/KDR and Flt-4 receptor activation and the release of NO. The protein levels of endothelial NO synthase (NOS) and inducible NOS were increased by HIV-1 Tat stimulation. Importantly, HIV-1 Tat caused apoptosis of HBMEC, as evidenced by changes in the cleavage of poly(A)DP-ribose polymerase, DNA laddering, and incorporation of fluorescein into the nicked chromosomal DNA (TUNEL assay). HIV-1 Tat-mediated apoptosis in HBMEC was significantly inhibited in the presence of N-nitro-l-arginine methyl ester (an inhibitor of NOS) and wortmannin (a phosphoinositol 3-kinase inhibitor). Furthermore, HIV-1 Tat treatment significantly increased HBMEC permeability, and pretreatment with both N-nitro-l-arginine methyl ester and wortmannin inhibited the Tat-induced permeability. Taken together, these results indicate that dysregulated production of NO by HIV-1 Tat plays a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB.

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Interactions between endothelial cells and HIV-1

Cited by 57 publications

References 191 publications

CCL16 activates an angiogenic program in vascular endothelial cells

CCL16 activates an angiogenic program in vascular endothelial cells

HIV-1 matrix protein p17 promotes angiogenesis via chemokine receptors CXCR1 and CXCR2

HIV-1 Tat-Mediated Apoptosis in Human Brain Microvascular Endothelial Cells

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