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C Pitzalis

Publications and source records attributed to C Pitzalis.

71 records · Page 4Linked to original sources
PubMed1989

Mechanisms of lymphocyte adhesion to endothelial cells: studies using a LFA-1-deficient cell line.

In order to investigate the role of lymphocyte function-associated antigen 1 (LFA-1) in lymphocyte adhesion to endothelial cells (EC), we have studied the adhesion of a LFA-1-deficient lymphoblastoid cell line, ICH-KM, which has < 10% of the cell surface LFA-1 expressed on a normal lymphoblastoid cell line, ICH-BJ. The adhesion of ICH-KM cells to unstimulated EC was 49.9 +/- 8.6% (mean +/- SD) that of ICH-BJ cells. Moreover, phorbol ester-stimulated ICH-KM cells showed a considerably weaker increase in adhesion to unstimulated EC compared with ICH-BJ cells (mean +/- SD increase in percentage adhesion, 3.8 +/- 2.3 compared with 18.5 +/- 8.0; P<0.025). In contrast, there was no significant difference between the enhanced adhesion of ICH-KM cells and ICH-BJ cells to interleukin-1 (IL-1)-stimulated EC. Thus ICH-KM cells showed a 22.7 +/- 11.0 (mean +/- SD) increase in percentage adhesion to IL-1-stimulated EC compared with the 24.8 +/- 8.5 increase in percentage adhesion of ICH-BJ cells. Anti-LFA-1 monoclonal antibodies had no effect on the enhanced adhesion of ICH-KM and ICH-BJ cells to IL-1-stimulated EC but abolished the differences in adhesion between the two cell lines. The study therefore indicates that although a major part of unstimulated and phorbol ester-stimulated lymphocyte-EC adhesion is dependent upon LFA-1, the enhanced adhesion due to stimulation of EC with IL-1 is not dependent upon this molecule. The data therefore supports the existence of cytokine-inducible LFA-1-independent adhesion molecules for lymphocytes on EC.

Antibodies, Monoclonal↗
PubMed1989

Rheumatoid T lymphocyte MHC class II expression: in vitro stimulation produces normal MHC class II expression, independent of proliferation.

MHC Class II mediated immune responses, such as tuberculin PPD, are often subnormal in rheumatoid arthritis (RA). We investigated peripheral blood T lymphocyte proliferation and Class II expression after stimulation with phytohemagglutinin, OKT3 and tuberculin PPD, using double label immunofluorescence and flow cytometry. No difference was found in the percentage of Class II positive T lymphocytes or intensity of fluorescence of Class II between matched controls and patients with RA. A disparity between Class II expression and proliferation was noted, particularly in the 50% of patients with RA with poor proliferation to PPD, who showed normal Class II expression, indicating that these 2 functions are under separate control.

Adult↗
PubMed1988

The preferential accumulation of helper-inducer T lymphocytes in inflammatory lesions: evidence for regulation by selective endothelial and homotypic adhesion.

The mechanisms which lead to the accumulation of T lymphocytes into inflammatory lesions are not clearly understood. We have previously shown that synovial CD4 T lymphocytes are mostly CDw29+UCHL1+ (helper-inducer cells) and very few carry the CD45R antigen which identifies the suppressor-inducer subset. Synovial CD8+ cells are also CDw29+UCHL1+CD45R-. In the present study, lymphocytes from pleural and peritoneal inflammatory infiltrates were shown to have a similar phenotypic pattern. Furthermore, it was demonstrated that the CDw29+UCHL1+ subset had a greater ability than CD45R+ cells to adhere to endothelial cells and to form homotypic clusters. Differential surface expression of LFA-1 on the two subsets was also shown, but this could not account for the demonstrated adhesion differences. Differences in adhesion between CDw29+/UCHL1+ and CD45R+ cells may explain the preferential accumulation of CDw29+/UCHL1+ cells in inflammatory infiltrates and underlie some of the functional differences between cells taken from sites of chronic inflammation and those from peripheral blood.

Antigens, Differentiation↗
PubMed1988

Abnormal helper-inducer/suppressor-inducer T-cell subset distribution and T-cell activation status are common to all types of chronic synovitis.

We have previously shown that rheumatoid synovial T cells are virtually all helper-inducer (CD4+4B4+UCHL1+) rather than suppressor-inducer (CD4+2H4+) cells. CD8 cells were also largely 4B4+. In addition, the majority of T cells were HLA-DR+. To investigate whether these findings were specific for rheumatoid disease, we studied the prevalence of these markers in a variety of chronic inflammatory arthropathies such as ankylosing spondylitis, Reiter's syndrome, and psoriatic arthritis. Again, almost 90% of the T cells were 4B4+UCHL1+ and only 11% were 2H4+; 50% expressed the HLA DR antigen. Thus this phenotypic distribution represents a final common pathway of chronic synovitis and may help to explain the immunopathology of the lesion.

HLA-D Antigens↗
PubMed1988

Correlation of immunoregulatory function with cell phenotype in cord blood lymphocytes.

The strong suppressor activity of cord T lymphocytes contrasts markedly with their mainly CD4 (helper) rather than CD8 (suppressor) phenotype. We studied the phenotype of cord CD3, CD4 and CD8 cells compared to adult cells using the monoclonal antibodies, 2H4, 4B4, and UCHL1. Almost all cord CD4 lymphocytes carried the suppressor-inducer marker 2H4, whereas 4B4+ UCHL1+ helper-inducer cells were virtually absent; CD8 cord cells were also of the 2H4+ 4B4- UCHL1- phenotype. In contrast in adult peripheral blood, half of the T cells, whether CD4 or CD8, were 2H4+ and half 4B4/UCHL1+. The suppressor-inducer phenotype of cord T cells was shown, in parallel functional experiments, to correlate with their enhanced proliferation to lectin and poor production of immunoglobulin and with the ability of cord mononuclear cells to suppress proliferation and immunoglobulin production by adult cells in co-culture experiments. These results indicate that the major imbalance in the cord CD4 subset in favour of 2H4 cells can explain many of the functional differences from adult cells. However, involvement of other cell types, in particular of the monocyte lineage, is necessary to explain other properties of immunocompetent cord cells.

Adult↗
PubMed1987

Abnormal distribution of the helper-inducer and suppressor-inducer T-lymphocyte subsets in the rheumatoid joint.

T lymphocytes can be divided into two main phenotypic populations, CD4 and CD8. These can be further subdivided into 2H4, 4B4, or UCHL1 subsets by appropriate monoclonal antibodies. We have investigated these subsets in the synovial fluid of patients with rheumatoid arthritis and have found (i) a virtual absence of CD4+ 2H4+ and the marked reduction of CD8+ 2H4+ T cells; (ii) a marked increase of CD4+ 4B4+ and CD8+ 4B4+ T cells; and (iii) a marked increase of CD4+ UCHL1+ and CD8+ UCHL1+ T cells compared with peripheral blood. Although the functions of the CD8 subsets are not known, the virtual absence of CD4+ 2H4+ suppressor-inducer T cells and the marked increase of CD4+ 4B4+ helper-inducer T cells and of CD4+ UCHL1+ memory T cells may help to explain the many known functional immunological properties of synovial T cells.

Antibodies, Monoclonal↗
PubMed1987

Abnormal lymphocyte reactivity to self-major histocompatibility antigens in rheumatoid arthritis.

Proliferation of rheumatoid and control peripheral blood mononuclear cells to OKT3, phorbol myristic acid (PMA), phytohemagglutinin (PHA), tuberculin PPD and in the autologous mixed lymphocyte reaction (AMLR) was investigated. Only the responses to PPD and in the AMLR were depressed. This was not due to suppression by OKT8 lymphocytes. The proportion of antigen responsive (T4+ 4B4+) cells was normal but suppressor-inducer (T4+ 2H4+) cells were decreased. The depressed response was not completely restored by addition of recombinant interleukin-2. We propose that a basic defect in rheumatoid arthritis resides in T lymphocytes which react to self-major histocompatibility complex antigens either on their own, as in the AMLR, or as restriction elements in the presentations of soluble antigen.

Adult↗
PubMed1987

Expression of HLA-DR, DQ and DP antigens and interleukin-2 receptor on synovial fluid T lymphocyte subsets in rheumatoid arthritis: evidence for "frustrated" activation.

Synovial fluid and peripheral blood T lymphocytes were examined from 10 patients with rheumatoid arthritis and 2 controls. T lymphocytes from inflammatory fluids were activated as shown by their increased size and expression of class II MHC antigens. Of the T cells, 60% were DR positive, 19% DP positive and 29% DQ positive. More Leu 2a than Leu 3a cells were HLA-DR positive. In contrast, few T cells expressed Tac. We conclude that T cell activation is taking place but is incomplete or "frustrated".

Adult↗
PubMed1986

Human retroplacental sera inhibit the expression of class II major histocompatibility antigens.

Since factor(s) present in human pregnancy sera may interfere with HLA-DR expression on antigen-presenting cells which could account for fetal immune tolerance, we decided to investigate HLA-DR expression on the human myeloid macrophage cell line U937 using the monoclonal antibody RF DR2 and flow cytometry. Following incubation of U937 cells with recombinant interferon gamma (rIFN gamma) and fetal calf serum, 76% of the cells were HLA-DR positive. In contrast, when U937 cells were incubated with retroplacental serum (RP) only 40% of them were positive for HLA-DR and the mean fluorescent intensity for the cell population was significantly diminished. By performing these experiments at 37 and at 4 degrees C we concluded that a factor or factors present in RP bind onto and mask class II major histocompatibility (MHC) antigen expression.

Cells, Cultured↗
PubMedDate not supplied

[Role of cell migration in the pathogenesis of rheumatoid arthritis: in vivo studies in SCID mice transplanted with human synovial membrane].

OBJECTIVE: Adhesion mechanisms play a central role in the recruitment of leukocytes which characteristically infiltrate rheumatoid synovium. Therefore, we adapted an animal model, in which human rheumatoid synovium was transplanted into severe combined immunodeficient (SCID) mice, to study the effects of Tumor Necrosis Factor-alpha (TNF-alpha) in modulatine leukocyte migration and to investigate the chemotactic potential of Stromal Derived Factor-1 alpha (SDF-1 alpha). MATERIALS AND METHODS: Human synovium samples, obtained from patients undergoing joint replacement, were divided into two parts. One was analysed by immunohistology and the other was implanted subcutaneously into SCID mice under general anaesthesia. Four weeks post-transplantation, grafts were injected with optimal dose of SDF-1, TNF-alpha or saline (negative control). At the same time, animals were injected iv with fluorescently labelled cells. 48 hours later mice were sacrificed and grafts removed for cryo-hystology. The number of cells migrating to the grafts was determined by UV-microscopy and the results expressed as cells per high power field. RESULTS AND CONCLUSIONS: In these studies we provide the evidence that: 1) the animal model, in which human tissues are grafted into SCID mice, can be used to study cell migration under controlled experimental conditions; 2) direct intragraft injection of TNF-alpha increases lymphocytes migration and up-regulates the expression of human adhesion molecules (CAMs) and 3) SDF-1 alphainjected intragraft increases the migration of the pro-myelo-monocytic U937 cells to synovial transplants, even more efficiently than TNF-alpha, but without modifications of CAMs' expression.

Animals↗
PubMedDate not supplied

[Glucocorticoids at the threshold of the new millennium: recent findings on the anti-inflammatory and immunomodulator mechanisms of action and future perspectives].

The aim of this work was to provide an updated review of the mechanisms of action of glucocorticoids. We carried out a MEDLINE search (1970 to present) using "glucocorticoids" as the keyword, both on its own (subheadings: "genetics, immunology, metabolism, physiology, therapeutic use") and combined with "inflammation", "glucocorticoid response element", "gene expression regulation", "NF-kappa B", "transcription factor AP-1", "receptors, glucocorticoid", "chemokines", "cytokines", "cytokine receptors", "resistance", "sensitivity", "annexin-I", "apoptosis", "repressors" and "activators", respectively. Original, partially unpublished data from our research group was also reported. Although we reviewed the sources available, we did not adopt any statistic procedures for data extraction, as the review deals only with basic research. The results of this review indicate that glucocorticoids act through different mechanisms: they can regulate the transcription of a number of genes (genomic mechanisms), interfere with cell activation factors (mechanisms of repression of cell activation factors), and inhibit cell activation via a direct interaction with the cell membrane and/or some of its components (non-genomic mechanisms). There is some evidence that most of the anti-inflammatory effects of glucocorticoids are mediated by repression of transcriptor factors, whereas their metabolic effects appear to be predominantly mediated by genomic mechanisms. This observation has prompted the search for new steroid compounds endowed with more selective anti-inflammatory properties than those currently available. We conclude that better understanding of the mechanisms of action of steroids may result in the development of new molecules with a better risk/benefit ratio.

Adjuvants, Immunologic↗
PubMedDate not supplied

Role of chemokines and chemokine receptors in regulating specific leukocyte trafficking in the immune/inflammatory response.

Antigen recognition, lymphocyte priming and effector responses in inflamed tissues depend on a coordinated and sequential series of events that take place in different anatomical compartments. The integration of these processes is favoured by the dynamic capacity of leukocytes to recirculate between the bloodstream and specific organs and to navigate inside the tissues in a programmed fashion, regulated by a complex interaction of cell adhesion molecules and soluble chemoattractants, in particular chemokines. In this review we discuss the role of chemokines and chemokine receptors in regulating leukocyte trafficking in different anatomical sites in the context of distinct functional phases of the immune/inflammatory response.

Autoimmune Diseases↗
PubMedDate not supplied

The role of interleukin-8 and other cytokines in the pathogenesis of Felty's syndrome.

OBJECTIVE: Felty's syndrome (FS) is defined as rheumatoid arthritis (RA) with neutropenia and, in some cases, splenomegaly; the outcome is primarily determined by the risk of infection, which is related to the degree of neutropenia. We analysed whether the clinical manifestations of FS, especially neutropenia, could be explained by abnormalities in cytokine production. METHODS: We examined the production in FS of five cytokines involved in the maturation and activation of polymorphonuclear cells (PMNs): IL-1 beta, TNF alpha, IL-8, G-CSF and GM-CSF. Because of the role of systemic IL-8 in neutrophil migration, serum IL-8 levels were also evaluated. RESULTS: Spontaneous and anti-CD16 stimulated cytokine production was similar in FS, RA and healthy controls (NC). However, anti-CD3 stimulated IL-8 production was significantly increased compared to NC in both RA and FS. FS patients who spontaneously produced G-CSF in culture were protected from bacterial infections. Serum IL-8 levels were elevated in FS and RA compared to NC (p < 0.001 for both groups). In FS, serum IL-8 was higher in patients with a history of bacterial infections compared to those without (p < 0.01) and there was a weak inverse correlation between neutropenia and serum IL-8 levels (Kendal's tau B = -0.31, p = 0.05). CONCLUSION: The neutropenia of FS cannot be explained by changes in peripheral blood cytokine production, although changes in the bone marrow microenvironment cannot be excluded. Our data do suggest a possible role for G-CSF and IL-8 in the development of certain FS complications.

Arthritis, Rheumatoid↗
PubMedDate not supplied

The sensitivity and specificity of reduced CD8 lymphocyte levels in the diagnosis of polymyalgia rheumatica/giant cell arteritis.

The aim of this study was to determine whether the sensitivity and specificity of measuring CD8+ T lymphocyte percentages and numbers could be diagnostically useful in the assessment of polymyalgia rheumatica/giant cell arteritis (PMR/GCA). Double immunofluorescence and FACScan analysis were used to identify and quantify the CD3+CD8+ lymphocyte population. The absolute cell numbers were determined by a Coulter Counter. Random disease controls were used for comparison with 30 patients diagnosed as PMR/GCA. Both the percentage of CD3+CD8+ cells (17.4% PMR/GCA group vs 30.5% control) and the absolute numbers of CD8+ lymphocytes (310 cell/ml PMR/GCA vs 723 cells/ml control) were significantly reduced (p < 0.001) in the PMR group. The sensitivity of reduced CD8+ percentages for diagnosis was 73% and the specificity was 85%. Analysis of likelihood ratios showed that CD8+ lymphocyte percentages < 22.15% were five times more likely in patients with PMR/GCA than in controls. Data suggested that reduced CD8+ lymphocyte levels may be useful in the initial clinical assessment of patients with PMR/GCA. Only a larger study can establish whether these parameters should be used as diagnostic criteria.

Aged↗
PubMedDate not supplied

Adhesion and migration of inflammatory cells.

Adhesion molecules play a major role in many biological functions. From the immunological point of view they are involved in virtually every process involving cell contact from thymic selection to antigen priming, from antigen recognition to cell activation, from cytotoxicity to lymphocyte recirculation. During an inflammatory process leucocyte migration represents one of the most important mechanisms of defense. At the site of the lesion inflammatory cells become activated and differentiate into effector cells. If the insult persists, mononuclear cells are retained in the attempt to clear the noxious stimulus. In this article the mechanisms of cell migration are reviewed together with the role of adhesion molecules in cell activation and local retention. Finally, the new therapeutic modalities against adhesion molecules are briefly considered.

Animals↗