Expression of VE (vascular endothelial)-cadherin and other endothelial-specific markers in haemangiomas.

Haemangiomas are vascular tumours characterized by rapid growth and increased endothelial turnover. VE-cadherin is a recently discovered endothelial cell-specific cadherin located at intercellular junctions. In different types of epithelial tumours, cadherin expression is inversely correlated with invasiveness and metastatic dissemination.

Thrombin-induced endothelial cell dysfunction.

Endothelium is a multifunctional organ which can directly influence circulating blood components as well as other cells within the vessel wall. The clotting enzyme thrombin, generated at the surface of damaged endothelium, induces blood coagulation but also exerts a variety of functional effects on the endothelium itself. Thrombin acts on endothelial cells to stimulate synthesis and release of various agents, such as inflammatory mediators, vasoactive substances and growth factors.

Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured human endothelial cells.

When cultivated on substrates that prevent cell adhesion (the polymer polyhydroxyethylmethacrylate, bovine serum albumin, and Teflon), human endothelial cells (EC) rapidly lost viability with a half-life of approximately 10 h. Dying EC showed the morphological and biochemical characteristics of apoptosis. The apoptotic process of suspended EC was delayed by the protein synthesis inhibitor cycloheximide.

Leukocyte-endothelial cell adhesive receptors.

The first step in leukocyte localization at inflammatory foci is their adhesion to the endothelial surface. This is a complex process mediated by several adhesive molecules expressed both on the leukocyte and endothelial membrane. In the early phases of inflammation, leukocytes transiently adhere to the vessel wall in a process termed "rolling".

Pro- and anti-inflammatory cytokines: interactions with vascular endothelium.

Cytokines elicit the expression of distinct sets of functions in endothelium. IL-1 activates endothelium in a prothrombotic-proinflammatory sense. The characteristics and significance of IL-1 inducible genes cloned from endothelial cells is discussed.

Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in undifferentiated nasopharyngeal carcinoma (lymphoepithelioma) and in malignant epithelial tumors.

Immunoreactivity for intercellular adhesion molecule-1 (ICAM-1) and for vascular cell adhesion molecule-1 (VCAM-1), two adhesion molecules of the immunoglobulin (Ig) superfamily, was tested and measured on tissue sections from 16 undifferentiated nasopharyngeal carcinomas (U-NPC), 12 keratinizing squamous cell carcinomas (SCCs) of the head and neck region, and 54 malignant epithelial tumors of various origin. Neoplastic cells of all cases of U-NPC were diffusely and intensely stained for ICAM-1 and VCAM-1. Moreover, ICAM-1 messenger RNA (mRNA) and VCAM-1 mRNA were detected by Northern blot analysis of RNA extracts from two tumors.

Clustering of vitronectin and RGD peptides on microspheres leads to engagement of integrins on the luminal aspect of endothelial cell membrane.

In previous work (Conforti et al, Blood 80:437, 1992), we have shown that integrins in endothelial cells (EC) are not polarized to the basal cell membrane, but are also exposed on the apical cell surface, in contact with blood. Therefore, endothelial integrins might be available for binding circulating plasma proteins. However soluble plasma vitronectin (vn) bound very poorly to EC apical surface and this interaction was unaffected by Arg-Gly-Asp (RGD) peptides or an anti-alpha v beta 3 serum.

Spatial and temporal relationships between cadherins and PECAM-1 in cell-cell junctions of human endothelial cells.

The integrity of the endothelial layer, which lines the entire cavity of the vascular system, depends on tight adhesion of the cells to the underlying basement membrane as well as to each other. It has been previously shown that such interactions occur via membrane receptors that determine the specificity, topology, and mechanical properties of the surface adhesion. Cell-cell junctions between endothelial cells, in culture and in situ, involve both Ca(2+)-dependent and -independent mechanisms that are mediated by distinct adhesion molecules.

Co-expression of endothelial cell and macrophage antigens in Kaposi's sarcoma cells.

The histopathogenesis of Kaposi's sarcoma (KS) was investigated using immunocytochemistry in 12 skin biopsies obtained from two AIDS patients, nine patients with the classic form, and one organ-transplant patient. KS cells revealed a peculiar antigenic profile, being characterized by co-expression of endothelial and macrophage markers. KS cells were stained for von Willebrand factor (vWF); for vascular endothelial (VE) cadherin, an endothelial specific adhesion molecule; and for PECAM/CD31.

A novel mechanism of colon carcinoma cell adhesion to the endothelium triggered by beta 1 integrin chain.

We have found a monoclonal antibody, called BV7, that rapidly stimulated by 6-10-folds HT-29 colon carcinoma cell adhesion to resting human umbilical vein endothelial cells. This effect was directed to tumor cells and not to endothelial cells and was cell-specific. BV7 was also active on the HCCP-2998 but did not change adhesion to endothelial cells of other tumor cells (MG63 osteosarcoma, A375 melanoma, MHCC-1410 and Lovo colon carcinoma) even if, by flow cytometry, this monoclonal antibody could bind to them.

Cell-surface plasminogen activation causes a retraction of in vitro cultured human umbilical vein endothelial cell monolayer.

Vascular endothelium forms a dynamic interface between blood and underlying tissues. Endothelial monolayer integrity is required for controlled vascular permeability and to preclude exposure of subendothelial cell matrix to circulating cells. Recent studies have established that cultured human umbilical vein endothelial cells (ECs) express receptors for plasminogen (plg) and urokinase-like plasminogen activator (uPA).

Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene.

1. The ability of the coumarin derivative cloricromene (8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy- carbonylmethoxycoumarin) to inhibit monocyte adhesion to human cultured umbilical vein endothelial cells (HUVEC) was investigated. 2.

IL-1 inducible genes in human umbilical vein endothelial cells.

In an attempt to understand more directly the molecular mechanisms involved in the cellular response of endothelial cells to Interleukin-1 (IL-1), we have made several cDNA libraries from human umbilical vein endothelial cells (HUVEC) stimulated for 1 h with IL-1 in the presence of cycloheximide. The cDNA libraries were differentially screened with labelled cDNA derived from mRNA isolated from untreated or IL-1 treated HUVEC. Forty cDNA clones induced by IL-1 were isolated and partially sequenced.

Decreased adhesion to endothelial cells and matrix proteins of H-2Kb gene transfected tumour cells.

Transfection of murine metastatic B78H1 cells (derived from B16 melanoma) with a syngeneic H-2Kb gene was used to study the effect of Major Histocompatibility Complex (MHC) gene products on tumour cell adhesion to endothelial cells and matrix proteins and the involvement in the metastatic process. H-2Kb-expressing transfectants showed a reduced adhesion to endothelial surfaces of different origin (four murine endotheliomas and human umbilical vein endothelial cells) when compared to parental B78H1 cells and to controls transfected with pSV2neo alone. On the average a 50-70% reduction in adhesion to endothelial cells was observed among H-2Kb transfectants.

Vascular activation in the histopathogenesis of Hodgkin's disease: potential role of endothelial tissue factor in intravascular thrombosis and necrosis.

Endothelial cell activation and alterations of intravascular coagulation were investigated in 27 cases of Hodgkin's disease (HD), in five cases of anaplastic large cell lymphoma (ALCL), and in ten reactive lymph nodes. Lymph node sections were immunostained for E-selectin, a molecule present on cytokine-activated endothelial cells; for tissue factor (TF), a cellular initiator of the coagulation cascade; for glycoprotein (gp) II/III, a platelet-specific antigen; and for fibrin. In HD, vascular activation was particularly prominent in the nodular sclerosis subtype, as indicated by a larger number of E-selectin-positive blood vessels (72 +/- 49) compared with mixed cellularity (22 +/- 37).

Endothelial cell-to-cell junctions. Structural characteristics and functional role in the regulation of vascular permeability and leukocyte extravasation.

Endothelial monolayer forms the main barrier to the passage of macromolecules and circulating cells from blood to tissues. This property is regulated by intercellular junctions. These are complex structures formed by transmembrane adhesive molecules linked to a network of cytoplasmic cytoskeletal proteins.

Endothelial cell migration and invasiveness are induced by a soluble factor produced by murine endothelioma cells transformed by polyoma virus middle T oncogene.

Polyoma virus middle T-transformed murine endothelioma cell lines provide a useful model for studying vascular lesions such as hemangiomas, hemangiosarcomas, and Kaposi's sarcoma and tumor-associated angiogenesis. In vivo they produce fast-growing, hemorrhaging, cavernous blood-filled hemangiomas, mainly formed by recruited host endothelial cells, suggesting an angiogenesis-like process underlying the lesion. The molecular mechanism(s) responsible for the recruitment of host endothelial cells by endothelioma cells has not yet been identified.

Platelet aggregation induced by the endoperoxide analogue U46619 is inhibited by polymorphonuclear leukocyte ADPase activity.

Platelet activation by the stable endoperoxide analogue U46619 is mediated largely by ADP released from platelet-dense granules. Polymorphonuclear leukocytes (PMNs) endowed with ecto-ADPase activity may operate as antiaggregatory cells in platelet aggregation induced by U46619. Unstimulated PMNs were effective in reducing aggregation when platelets were stimulated by threshold concentrations of U46619, whereas at higher concentrations of the stimulus, PMN activation is required.

Immunoelectron characterisation of the inter-endothelial junctions of human term placenta.

The molecular constituents of the paracellular clefts in human placental microvessels were investigated using antibodies against PECAM-1, pan-cadherin, A-CAM (N-cadherin), cadherin-5 and two types of integrins (those recognised by antibodies to the beta 1 chain and alpha v beta 3). Ultrastructural localisation of these molecules in ultrathin frozen sections of human term placentae was attempted using colloidal gold immunocytochemistry, after establishing their presence by indirect immunofluorescence. At the light microscopical level, the endothelial paracellular clefts were found to be immunoreactive to the antibodies against PECAM-1, cadherin-5 and pan-cadherin, but not the integrins.

Inhibition of cytokine production and endothelial expression of adhesion antigens by 5'-methylthioadenosine.

We investigated the activity of endogenous nucleoside 5'-deoxy-5'-methylthioadenosine (MTA) on both the production of inflammatory cytokines and the cytokine-dependent endothelial expression of adhesion molecules. The compound inhibited the production of tumor necrosis factor (but not interleukin-1) in lipopolysaccharide-activated macrophages. In addition, MTA selectively inhibited the expression of intercellular adhesion molecule-1 in endothelial cells activated with interleukin-1.

CD34 expression is regulated reciprocally with adhesion molecules in vascular endothelial cells in vitro.

Freshly cultured vascular endothelial cells express the CD34 antigen in a diffuse cell surface pattern with some concentration on microvilli. Expression is downregulated with proliferation in continuous culture and undetectable after nine population doublings but can be maintained by restraining cell proliferation and promoting cell contact. Expression of CD34 at the antigen and mRNA levels on early passage cells is rapidly downregulated by interleukin-1 beta (IL-1 beta), interferon-gamma (INF-gamma), and tumor necrosis factor-alpha (TNF-alpha) under conditions in which these ligands upregulate the adhesion molecules: endothelial leukocyte adhesion molecule 1 (ELAM-1) and intracellular adhesion molecule 1 (ICAM-1).

Effect of heparin, dermatan sulfate, and related oligo-derivatives on human polymorphonuclear leukocyte functions.

The in vitro effect of unfractionated heparin and dermatan sulfate, as well as oligo-heparin and oligo-dermatan sulfate, on human PMN function was investigated. Superoxide anion generation in fMLP-stimulated PMN was dose-dependently reduced by heparin and oligo-heparin, while DS and oligo-DS lacked inhibitory activity. FMLP-stimulated PMN adhesion to endothelial cells was reduced to a similar extent by both heparin and oligo-heparin, but not by DS and oligo-DS.