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Biomedical subjects

D Ribatti

Publications and source records attributed to D Ribatti.

At least 37 records · Page 2Linked to original sources
PubMed2005

Do mast cells affect villous architecture? Facts and conjectures.

In adult life, the architecture of the intestinal villus is maintained by a complex series of epithelial-stromal interactions that involve different types of fixed and mobile cells located in the intestinal mucosa. Mast cells (MC) are normal constituents of the small bowel mucosa where they reside in the villous and pericryptal lamina propria as well as within the columnar epithelial cell layer. Besides being involved in numerous immune and inflammatory reactions in the context of both innate and acquired host defence, MC are known to exert important non-immunological functions like wound repair, extracellular matrix remodelling, angiogenesis and neurotrophism as well as modulation of fibroblast, epithelial cell and smooth muscle cell activity. These pleiotropic functions put MC in a central, strategic position to organize tissue defence, restore tissue damage and maintain tissue homeostasis. This review summarizes the most recent advances concerning the functional anatomy of the crypt-villus unit and discusses the way intestinal MC might become part of the instructive circuits that ultimately lead to the maintenance of a proper villous shape.

Animals↗
PubMed2005

Endothelial progenitor cells in health and disease.

There is currently great excitement and expectation in the stem cell community following the discovery that multipotent stem cells can be cultured from human fetal tissue and retain their ability to give rise to a variety of differentiated cell types found in all three embryonic germ layers. Although the earliest sites of hematopoietic cell and endothelial cell differentiation in the yolk sac blood islands were identified about 100 years ago, cells with hemangioblast properties have not yet been identified in vivo. Endothelial cells differentiate from angioblasts in the embryo and from endothelial progenitor cells, mesoangioblasts and multipotent adult progenitor cells in the adult bone marrow. Circulating endothelial progenitor cells (EPC) have been detected in the circulation after vascular injury and during tumor growth. The molecular and cellular mechanisms underlying EPC recruitment and differentiation are not yet understood, and remain as one of the central issues in stem cell biology. For many years, the prevailing dogma stated that the vessels in the embryo develop from endothelial progenitors, whereas sprouting of vessels in the adult results only from division of differentiated endothelial cells. Recent evidence, however, indicates that EPC contribute to vessel growth in the embryo and in ischemic, malignant or inflammed tissues in the adult, and can even be therapeutically used to stimulate vessel growth in ischemic tissues.

Animals↗
PubMed2004

The thymus is a site of mast cell development in chicken embryos.

Thymic mast cells were studied by light and transmission electron microscopy in chicken embryos during organogenesis. Mast cells made their first appearance at day 15. At days 16 and 17, there was a burst of mast cell development with a peak of 278 +/- 54 cells/mm(2) at day 16. Then, mast cell density decreased until hatching. During the whole embryonic period, about 80% of mast cells localized to the thymic medulla. In the cortex, they were less numerous, and some rare mast cells could be identified in the capsule and septa. Thymic mast cells could be recognized in association with hematopoietic foci, but frequently they grew independently from areas of hematopoiesis and appeared as single cells interspersed among thymocytes, thymic epithelial cells, and interdigitating cells. They were often recognized in close relationship with the scanty and delicate extracellular matrix of the developing gland. Viewed by electron microscopy, mast cells were relatively small cells, with a few secretory granules. Exocytosis was never seen, but, notably, granules emptied in a piecemeal degranulation fashion. This study demonstrates that the chicken thymus is a site of mast cell development during embryogenesis. The high mast cell density we found suggests a possible role for these cells during thymus organogenesis.

Animals↗
PubMed2004

A novel RGDS-analog inhibits angiogenesis in vitro and in vivo.

In this study the anti-angiogenic action of a novel non-peptide RGDS-analog named RAM was tested in vitro and in vivo. RAM inhibited FGF-2-induced chemotaxis by 80% in an adhesion-independent way. Further, it induced HUVEC-apoptosis in collagen-seeded HUVEC, indicating that such pro-apoptotic effect was adhesion-independent. In vivo studies revealed that RAM inhibited FGF-2 induced angiogenesis by 60% in the mouse Matrigel-assay and in the chicken-egg chorion-allantoic membrane assay. Finally, RAM was markedly more stable in serum as compared to the template RGDS and after 24 h incubation in 100% serum was significantly more active than RGDS. Taken together these results show that RAM exerts anti-chemotactic and pro-apoptotic effects, by an unexpected adhesion-independent mechanism, as we have recently shown for the template RGDS molecule [Blood 103 (2004) 4180], and has in vivo relevant anti-angiogenic properties, with marked stability in serum; therefore, RAM represents a novel promising anti-angiogenic molecule.

Angiogenesis Inhibitors↗
PubMed2004

Antiangiogenic activity of aplidine, a new agent of marine origin.

The antineoplastic compound aplidine, a new marine-derived depsipeptide, has shown preclinical activity in vitro on haematological and solid tumour cell lines. It is currently in early phase clinical trials. The exact mechanism of action of this anticancer agent still needs to be clarified. We have previously reported that aplidine blocks the secretion of the angiogenic factor vascular endothelial growth factor (VEGF) by the human leukaemia cells MOLT-4, suggesting a possible effect on tumour angiogenesis. This study was designed to investigate the antiangiogenic effect of aplidine. In vivo, in the chick embryo allantoic membrane (CAM) assay, aplidine inhibited spontaneous angiogenesis, angiogenesis elicited by exogenous VEGF and FGF-2, and induced by VEGF overexpressing 1A9 ovarian carcinoma cells. In vitro, at concentrations achievable in the plasma of patients, aplidine inhibited endothelial cell functions related to angiogenesis. It affected VEGF- and FGF-2-induced endothelial cell proliferation, inhibited cell migration and invasiveness assessed in the Boyden chamber and blocked the production of matrix metalloproteinases (MMP-2 and MMP-9) by endothelial cells. Finally, aplidine prevented the formation of capillary-like structures by endothelial cells on Matrigel. These findings indicate that aplidine has antiangiogenic activity in vivo and inhibits endothelial cell functional responses to angiogenic stimuli in vitro. This effect might contribute to the antineoplastic activity of aplidine.

Angiogenesis Inhibitors↗
PubMed2004

A possible role of tryptase in angiogenesis in the brain of mdx mouse, a model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and affects the CNS. Dystrophin is absent in muscle and CNS of both DMD patients and mdx mouse, a model of DMD. While the involvement of vascular compartment in DMD was poorly investigated, some studies suggested a role for mast cells (MC). Tryptase, contained in the MC granules, stimulates angiogenesis in vitro and in vivo. We demonstrated for the first time a correlation between the extent of angiogenesis and the number of tryptase-positive neurons and microvessels and suggest that the tryptase contained in the neurons and in the endothelial cells of the mdx mouse brain may be involved in the regulation of angiogenesis taking place in mdx mouse.

Animals↗
PubMed2004

Altered blood-brain barrier development in dystrophic MDX mice.

In order to ascertain whether the alterations of the blood-brain barrier (BBB) seen in adult dystrophic mdx-mice [Glia 42 (2003) 235], a human model of Duchenne muscular dystrophy (DMD), are developmentally established and correlated with other dystrophin isoforms which are localized at the glial-vascular interface, we used immunocytochemistry to investigate the expression of dystrophin isoforms (Dp71) during BBB development in mdx fetuses and in adult mice. Parallelly, we used Western blot, immunocytochemistry and immunogold electron microscopy to analyze the expression of the zonula occludens (ZO-1), aquaporin-4 (AQP4) and glial fibrillary acidic (GFAP) proteins as endothelial and glial markers, and we evaluated the integrity of the mdx BBB by means of intravascular injection of horseradish peroxidase (HRP). The results show reduced dystrophin isoforms (Dp71) in the mdx mouse compared with the control, starting from early embryonic life. Endothelial ZO-1 expression was reduced, and the tight junctions were altered and unlabeled. AQP4 and GFAP glial proteins in mdx mice also showed modifications in developmental expression, the glial vascular processes being only lightly AQP4- and GFAP-labeled compared with the controls. Confocal microscopy and HRP assays confirmed the alteration in vessel glial investment, GFAP perivascular endfoot reactivity being strongly reduced and BBB permeability increasing. These results demonstrate that a reduction in dystrophin isoforms (Dp71) at glial endfeet leads to an altered development of the BBB, whose no-closure might contribute to the neurological dysfunctions associated with DMD.

Animals↗
PubMed2004

Recombinant human erythropoietin induces intussusceptive microvascular growth in vivo.

The role of erythropoietin (Epo) in angiogenesis has not been completely clarified. Epo induces endothelial cell proliferation and migration and stimulates angiogenesis on rat aortic rings in vitro and in vivo in the chick embryo chorioallantoic membrane (CAM) assay. The aim of the present study was to evaluate the ultrastructural aspects of angiogenesis in the CAM vasculature after recombinant human Epo (rHuEpo) exposure. The results demonstrated that after rHuEpo stimulation, the generation of new blood vessels occurred more frequently following an intussusceptive microvascular growth (IMG) mechanism. We have performed our experiments between days 8 and 12 of incubation, that is, when in the normal condition the capillary network expands mainly by IMG, and because it is generally accepted that implants made from days 8 to 10 are strongly angiogenic. This response is peculiar of rHuEpo, because it is abolished when an Epo-blocking antibody was coadministered with Epo.

Animals↗
PubMed2004

Crosstalk between angiogenesis and lymphangiogenesis in tumor progression.

Extensive studies have identified reliable markers of lymphatic endothelial cells, and mechanisms and molecules that regulate development and growth of the lymphatic vessels. Vascular endothelial growth factors (VEGF)-C and VEGF-D, and their cognate receptor tyrosine kinase, VEGF receptor-3 (VEGFR-3), are critical regulators of lymphangiogenesis. By binding to its endothelial cell surface receptors VEGFR-1 and VEGFR-2, VEGF-A mediates vascular leakage, endothelial proliferation and migration. Angiopoietin-2 (Ang-2) is expressed at sites of blood vessel remodeling and invasion, and factors that induce angiogenesis in vivo, such as VEGF-A, upregulate Ang-2 in endothelial cells. In this review, we summarize the literature concerning the crosstalk between angiogenesis and lymphangiogenesis in tumor progression, that is, involvement of VEGF-C, VEGF-D and VEGFR-3 in angiogenesis, and the role played by VEGF-A and Ang-2 in lymphangiogenesis, respectively.

Humans↗
PubMed2004

Mast cell contribution to angiogenesis related to tumour progression.

The current wisdom is that tumours are endowed with an angiogenic capability and that their growth, invasion and metastasis are angiogenesis dependent. It is now well documented that neoplastic cells are influenced by their microenvironment and vice versa. The specific organ microenvironment determines the extent of cancer cell proliferation, angiogenesis, invasion and survival. Tumour cells are surrounded by an infiltrate of inflammatory cells, namely lymphocytes, neutrophils, macrophages and mast cells (MCs), which communicate via a complex network of intercellular signalling pathways, mediated by surface adhesion molecules, cytokines and their receptors. This review article summarizes: (i) the MC mediators involved in angiogenesis; (ii) the experimental evidence concerning the role played by MCs in angiogenesis; (iii) the list of solid and haematological tumours in which a close relationship between angiogenesis, tumour progression and MCs has been demonstrated; (iv) the circumstances in which MCs are a critical source of angiogenic factors in vivo, and in such cases, the signals that regulate their production and secretion that need to be determined as a prelude to the elaboration of new therapeutic strategies associated with MC presence and activation.

Angiogenesis Inducing Agents↗
PubMed2004

The mast cell: an active participant or an innocent bystander?

Mast cells (MC) are phylogenetically old cells which are distributed throughout the human organism and, on the whole, occupy roughly the volume of the spleen. MC have long been recognized as key cells of type I hypersensitivity reactions. Several lines of evidence, however, indicate that they not only express critical effector functions in classic IgE-associated allergic disorders, but also play important roles in host defence against parasites, bacteria and perhaps even viruses. Indeed, it is now clear that MC can contribute to host defence in the context of either acquired or innate immune responses through the release of a myriad of pro-inflammatory and immunoregulatory molecules and the expression of a wide spectrum of surface receptors for cytokines and chemokines. Moreover, there is growing evidence that MC exert distinct non-immunological functions, playing a relevant role in tissue homeostasis, remodeling and fibrosis as well as in the processes of tissue angiogenesis. In this review, we provide a small insight into the biology of human MC and their potential implications in clinical pathology.

Animals↗
PubMed2003

Serum cholesterol and impulsivity in a large sample of healthy young men.

Studies that have investigated the association between cholesterol levels and impulsivity are relatively few in number and have yielded equivocal results. In this study, we investigated the relationship between impulsivity, depression and serum lipids [total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides] in a large sample (N=2051) of healthy young men who were remarkably homogeneous in terms of age, educational level, and socioeconomic conditions. Depression was assessed using the depression scale of the Minnesota Multiphasic Personality Inventory-2, and impulsivity was measured using the impulse control scale of the Big Five Questionnaire (BFQ). We found that subjects with a low serum cholesterol, defined as the lowest tenth of the total cholesterol distribution (< or =3.7 mmol/l), scored significantly lower on the impulse control scale of the BFQ. There was no significant association between depression and cholesterol concentrations. In addition, in a multiple regression model, both lower levels of total cholesterol and higher levels of HDL cholesterol emerged as significant predictors of impulsivity. However, since the regression model accounted for only 0.6% of the variance in the score on the impulse control scale of the BFQ, the biological significance of these correlations was negligible. Taken together, these findings suggest that, in healthy young men, a relationship between cholesterol and impulsivity emerges only when the statistical analysis focuses on subjects with very low levels of cholesterol.

Adult↗
PubMed2003

Neovascularisation, expression of fibroblast growth factor-2, and mast cells with tryptase activity increase simultaneously with pathological progression in human malignant melanoma.

Tissues from 92 proliferative lesions of the melanocytic lineage defining distinct steps in tumour progression were investigated immunohistochemically for changes in angiogenesis, expression of fibroblast growth factor-2 (FGF-2) and density of total mast cells (MCs) and MCs expressing tryptase, an angiogenic-inducing molecule. Although the microvessel number was low in common nevi, it increased significantly in nevi with architectural disorder with varying degrees of melanocytic atypia (termed 'nevi with ADMA'), and these changes persisted during tumour development. Progression of primary melanomas was accompanied by a high microvessel number, and the progression to metastases by another significant increase in the microvessel counts. Expression of FGF-2, evaluated as percentages of positive lesions and positive cells per lesion was upregulated in the course of progression. Changes in expression were associated with nevi with ADMA, tumour changeover, penetration of the tumour into the dermis and metastases. A high correlation was demonstrated in all groups of tissues between the microvessel counts, percentages of FGF-2-positive tumour cells, and both total metachromatic and tryptase-reactive MCs. These results suggest that angiogenesis in human melanoma increases with tumour progression and that FGF-2 secreted by tumour cells and tryptase secreted by host MCs cooperate in its induction.

Adult↗
PubMed2003

New non-angiogenesis dependent pathways for tumour growth.

The current wisdom is that tumours are endowed with an angiogenic capability and that their growth, invasion and metastasis are angiogenesis-dependent. This article summarises the literature concerning recent histomorphological studies that indicate that some tumours may be vascularised without significant angiogenesis, probably by using existing vessels, a process later described as vascular co-option, or even by forming vascular channels on their own through a non-endothelial cell process called "vascular mimicry". Moreover, the possibility that bone marrow-derived stem cells may also be a source of endothelial precursor cells recruited for tumour-induced neovascularisation, is reviewed. In fact, it has been assumed that the additional endothelial cells required to construct new tumour vessels come from the division and proliferation of local endothelial cells and that endothelial cells incorporated into sites of neovascularisation, including tumour-induced new blood vessels, may be derived from these precursor cells. Finally, lymphoangiogenesis as a mechanism of de novo formation of lymphatics, favouring the metastatic dissemination of tumour cells, is summarised. Potential therapeutic applications are also discussed.

Bone Marrow Cells↗
PubMed2003

Vascular endothelial growth factor and its receptors in multiple myeloma.

Multiple myeloma (MM) progresses from an avascular to a vascular phase (active MM) accompanied by a significant increase in microvessel density in the bone marrow. This article summarizes the literature concerning the specific role played by vascular endothelial growth factor (VEGF) in this process. Recent applications of antiangiogenic agents that interfere with VEGF signaling and block MM progression are also described.

Angiogenesis Inhibitors↗