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M Uguccioni

Publications and source records attributed to M Uguccioni.

At least 19 recordsLinked to original sources
PubMed2003

Expression of CS-1 fibronectin precedes monocyte chemoattractant protein-1 production during elicitation of allergic contact dermatitis.

BACKGROUND: Leucocyte migration within inflammatory skin compartments in allergic contact dermatitis (ACD) is the result of a sophisticated multi-step event where multiple molecules are involved. OBJECTIVE: Since non-antigen-specific mechanisms have been described as an early participant in elicitation of ACD, we investigated the kinetics of the expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and the type of infiltrating cells. We compared the time course production of MCP-1/CCL2 with connecting segment-1 (CS-1) fibronectin and thymus and activation-regulated chemokine (TARC/ CCL17) expression. METHODS: Biopsies from 10 individuals challenged in their back with the antigen responsible for their contact dermatitis and an irrelevant antigen were taken at different times and histology, immunohistochemistry for CS-1 fibronectin, TARC/CCL17, CD3, CD68, CXCR3, CCR4 and in situ hybridization for MCP-1/CCL2 were performed. RESULTS: At positive antigen stimulated sites expression of MCP-1/CCL2 by basal keratinocytes and isolated cells in dermis started at 10 h. CS-1 fibronectin and TARC/CCL17 expression by blood endothelial cells was found at 2 and 10 h, respectively. This was followed by dermal accumulation of mononuclear cells with a significant increase of CD3+ and CD68+cells. At 48 h, approximately 58% of infiltrating cells were CXCR3+, and 35% CCR4+. CONCLUSIONS: We showed evidence of the fact that CS-1 fibronectin expression precedes the production of MCP-1/CCL2 and TARC/CCL17 in the skin of patients with ACD, suggesting that these molecules participate in the early complex process of migrating mononuclear cells during elicitation of ACD.

Adult↗
PubMed2002

[Advantages and limitations of the cardiovascular risk charts].

The absolute risk of cardiovascular events depends on the individual's global risk profile, obtained from estimating the effects of multiple risk factors in the subject. Several risk charts have been prepared by National Societies to calculate the probability of an individual to suffer coronary events during a 10-year follow-up period. In 1998 the Joint Task Force of the European Society of Cardiology published a risk chart which was diffused to promote primary prevention in the general population. However, some limitations apply to this model in Italy because the Framingham Study equation, which was implemented jointly by AHA/ACC for the assessment of cardiovascular risk, works in high risk North American populations but may overestimate risk in Mediterranean countries. On the other hand, the Carta Italiana del Rischio Cardiovascolare, derived successively from 3 different heterogeneous clinical studies to describe the risk profile, calculates the total cardiovascular burden in our population. The main advantage of introducing risk charts is the spread of prevention in the general population to reduce excess risk (> 20%) through suitable treatment. Thus, the assessment of high risk subjects warrants significant economic resources, and so it is important that it be appropriate. The Osservatorio Epidemiologico Cardiovascolare has collected data on the prevalence of cardiovascular risk factors in Italy, which could be easily integrated for a risk calculation appropriate to our country.

Cardiovascular Diseases↗
PubMed2001

CD antigens 2001.

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Antigens, CD↗
PubMed2001

Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5.

Eotaxin is a potent inducer of eosinophil chemotaxis and was considered as a selective ligand of the CC chemokine receptor 3 (CCR3), which is expressed on eosinophils, basophils, and Th2 lymphocytes. This study shows that eotaxin also interacts with CCR2 and CCR5 and can, thus, affect the responses of monocytes, which express both receptors. In human monocytes pretreatment with eotaxin decreased responsiveness to MCP-1, a selective ligand for CCR2, as well as to RANTES and MIP-1 beta, which bind to CCR5. Similar effects were obtained with transfected cells expressing CCR2 or CCR5, but here a difference became apparent: Eotaxin triggered CCR5 at a concentration of 100 nM but not CCR2 even at 1 microM, suggesting an antagonistic effect on this receptor. In agreement with this observation, eotaxin induced internalization of CCR5 but not of CCR2 in human monocytes and transfected cells. Binding studies showed that eotaxin displaces (125) I-MCP-1 from monocytes in a concentration-dependent manner, and functional experiments showed that eotaxin inhibits MCP-1-induced chemotaxis and enzyme release. The results demonstrate that eotaxin is a CCR5 agonist and a CCR2 antagonist. The present findings suggest a role of eotaxin in the fine-tuning of cellular responses occurring at sites of allergic inflammation, in which both MCP-1 and eotaxin are produced. (Blood. 2001;97:1920-1924)

Calcium Signaling↗
PubMed2001

CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease.

Lymph nodes with Hodgkin disease (HD) harbor few neoplastic cells in a marked leukocytic infiltrate. Since chemokines are likely to be involved in the recruitment of these leukocytes, the expression of potentially relevant chemokines and chemokine receptors were studied in lymph nodes from 24 patients with HD and in 5 control lymph nodes. The expression of regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta was analyzed by in situ hybridization and that of CCR3 and CCR5 by immunohistochemistry and flow cytometry. It was found that, overall, the expression of all 4 chemokines was markedly enhanced, but the cellular source was different. RANTES was expressed almost exclusively by T cells whereas the expression of MCP-1, MIP-1alpha, and MIP-1beta was confined largely to macrophages. In control lymph nodes, chemokine expression was low, with the exception of MIP-1alpha in macrophages. CCR3 and CCR5 were highly expressed in T cells of HD involved but not of control lymph nodes. CCR3 was equally distributed in CD4+ and CD8+ cells, but CCR5 was associated largely with CD4+ cells. In HD lymph nodes, CCR3 and CCR5 were also expressed in B cells, which normally do not express these receptors. All these chemokines and receptors studied, by contrast, were absent in the neoplastic cells. It was concluded that chemokines are involved in the formation of the HD nonneoplastic leukocytic infiltrate. Expression of CCR3 and CCR5 appears to be characteristic of HD, but the roles of these receptors' up-regulation for the disease process remain unclear.

Adult↗
PubMed2001

CD antigens 2001.

The most recent Human Leucocyte Differentiation Antigen Workshop ("HLDA7") took place in 2000 in Harrogate, UK and the proceedings are about to be published (Leucocyte Typing VII). New Sections were introduced in this Workship (Dendritic cells, Stem/progenitor cells, Erythroid cells and Carbohydrate Structures) and monoclonal antibodies were selected for which at least some molecular data were already available (to avoid "blind" screening of reagents against known specificities). A total of more than 80 new CD specificities were established (previously the average was less than 30 new CD specificities per Workshop) and these are listed in this article. There is already evidence for the existence of many new leucocyte surface molecules for study at the next HLDA Workshop (in Adelaide in 2004), and we have listed in this article a number of such potential CD candidates (identified following the production of monoclonal antibodies or via gene cloning). There are also today an increasing number of lineage- and/or stage-restricted leucocyte-associated molecules localised within the cell cytoplasm (or nucleus): they will certainly prove of intense in the future for many laboratories studying human haematopoietic cells (regardless of whether a new "intracellular CD" categorisation scheme is devised for such molecules).

Antigens, CD↗
PubMed2001

CD antigens 2001.

Explore the source record for details and available documents.

Antibodies, Monoclonal↗
PubMed2001

CD antigens 2001.

Explore the source record for details and available documents.

Antigens, CD↗
PubMed2001

Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity.

Endothelial cell receptors for the angiostatic chemokines IFN-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by IFN-gamma (Mig) have not yet been identified, and the mechanisms responsible for the effects of these chemokines on angiogenesis are still unclear. IP-10 and Mig share a common functional receptor on activated T lymphocytes, named CXC chemokine receptor 3 (CXCR3). Using in situ hybridization and immunohistochemistry, we show that CXCR3 is expressed by a small percentage of microvascular endothelial cells in several human normal and pathological tissues. Primary cultures of human microvascular endothelial cells (HMVECs) likewise express CXCR3, although this expression is limited to the S/G2-M phase of their cell cycle. Both IP-10 and Mig, as well as the IFN-gamma-inducible T-cell alpha chemoattractant (I-TAC), which all share high-affinity binding for CXCR3, block HMVEC proliferation in vitro, an effect that can be inhibited by an anti-CXCR3 antibody. These data provide definitive evidence of CXCR3 expression by HMVEC and open new avenues for therapeutic interventions in all conditions in which an angiostatic effect may be beneficial.

Angiogenesis Inhibitors↗
PubMed2001

CD antigens 2001.

This paper reviews the Seventh Human Leucocyte Differentiation Antigen (HLDA7) workshop. Due to the limitations of "blind" antibody screening, which had been evident at the previous meeting in 1996, participants at HLDA7 adopted a more selective approach to the choice of antibodies by identifying new CD specificities. This resulted in the addition of more than 80 new CD specificities. Plans for the eighth and subsequent workshops are also previewed.

Antibodies, Monoclonal↗
PubMed2000

Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation.

HIV particles that use the chemokine receptor CXCR4 as a coreceptor for entry into cells (X4-HIV) inefficiently transmit infection across mucosal surfaces [1], despite their presence in seminal fluid and mucosal secretions from infected individuals [2] [3] [4]. In addition, although intestinal lymphocytes are susceptible to infection with either X4-HIV particles or particles that use the chemokine receptor CCR5 for viral entry (R5-HIV) during ex vivo culture [5], only systemic inoculation of R5-chimeric simian-HIV (S-HIV) results in a rapid loss of CD4(+) intestinal lymphocytes in macaques [6]. The mechanisms underlying the inefficient capacity of X4-HIV to transmit infection across mucosal surfaces and to infect intestinal lymphocytes in vivo have remained elusive. The CCR5 ligands RANTES, MIP-1alpha and MIP-1beta suppress infection by R5-HIV-1 particles via induction of CCR5 internalization, and individuals whose peripheral blood lymphocytes produce high levels of these chemokines are relatively resistant to infection [7] [8] [9]. Here, we show that the CXCR4 ligand stromal derived factor-1 (SDF-1) is constitutively expressed by mucosal epithelial cells at sites of HIV transmission and propagation. Furthermore, CXCR4 is selectively downmodulated on intestinal lymphocytes within the setting of prominent SDF-1 expression. We postulate that mucosally derived SDF-1 continuously downmodulates CXCR4 on resident HIV target cells, thereby reducing the transmission and propagation of X4-HIV at mucosal sites. Moreover, such a mechanism could contribute to the delayed emergence of X4 isolates, which predominantly occurs during the later stages of the HIV infection.

Chemokine CXCL12↗
PubMed2000

Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C-C chemokines.

OBJECTIVE: Human chondrocytes produce different C-X-C and C-C chemokines under basal conditions and upon activation with proinflammatory cytokines. We investigated whether human chondrocytes also have chemokine receptors and examined the effects of chemokines on chondrocyte activity. METHODS: The expression of chemokine receptors was determined by immunochemical analysis of frozen sections from normal and osteoarthritic cartilage and by flow cytometry of isolated cells. The messenger RNA expression for chemokine receptors was studied by reverse transcriptase-polymerase chain reaction. Isolated chondrocytes were stimulated with different chemokines, and the responses were evaluated by assaying the release of matrix metalloprotease 3 (MMP-3) and of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase in the supernatants. RESULTS: A wide variety of chemokine receptors (CCR-1, CCR-2, CCR-3, CCR-5, CXCR-1, and CXCR-2) was detected on human chondrocytes. Interaction of these receptors with the corresponding ligands induced the release of MMP-3. This response was abrogated by pretreatment of the cells with Bordetella pertussis toxin, demonstrating involvement of G proteins of the Gi type. The response decreased in the presence of cycloheximide, indicating dependence on protein synthesis. Chemokines also induced the exocytosis of N-acetyl-beta-D-glucosaminidase, which was prevented by receptor blockage with anti-CCR-3 and by treatment with B pertussis toxin. Chondrocytes obtained from osteoarthritic tissue showed an increased expression of CCR-3 and possibly of CXCR-1, and an augmented release of matrix-degrading enzymes compared with chondrocytes from normal donors. CONCLUSION: Our findings suggest the existence in human chondrocytes of a novel catabolic pathway, primed by chemokines and their receptors, that leads to the breakdown of cartilage matrix components.

Acetylglucosaminidase↗