Search PubMed⌕ Search

Biomedical subjects

S Antonaci

Publications and source records attributed to S Antonaci.

At least 55 records · Page 3Linked to original sources
PubMed1998

Evaluation of monocyte chemotactic responsiveness in uraemic patients undergoing haemodialysis with different dialytic membranes.

Recent data show that monocyte chemotactic peptide-1 (MCP-1), a chemotactic factor specific for monocytes, may play a central role in regulating the activation of these cells. For this reason, the production of MCP-1 in peripheral blood mononuclear cell (PBMC) cultures of eight healthy subjects, six chronic uraemic subjects under conservative treatment and six chronic uraemic patients undergoing haemodialysis (HD), was assessed. In the latter group of individuals, complement-activating membranes such as cuprophan (CU) were used for 1 month followed by biocompatible non-complement-activating membranes, like polymethylmetacrylate (PMMA) for the next 30 days. The chemotactic index (CI) elicited by PBMC supernatants from patients undergoing dialysis was found to be significantly higher than that obtained by supernatants recovered from normal subjects or uraemic patients on conservative therapy. Furthermore, the CI from PBMC supernatants having had contact with CU membranes was higher than that obtained from PBMC activated by PMMA. Finally, the increased chemotactic ability in the supernatants was closely correlated with the augmented MCP-1 gene expression and production, as assessed by in vitro hybridization studies.

Adult↗
PubMed1997

In vitro production of tumor necrosis factor-alpha, interleukin-6 and interleukin-8 from normal human peripheral blood mononuclear cells stimulated by Rhodococcus equi.

The capability of heat-killed Rhodococcus equi organisms to induce in vitro release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 from normal human mononuclear cells as well as the secretion kinetics of these inflammatory cytokines over a 48 h period were evaluated. Results show that normal human mononuclear cells are efficiently triggered to secrete TNF-alpha, IL-6 and IL-8 following R. equi stimulation according to a different kinetics. In particular, release of IL-B was already maximally expressed after 2 h of stimulation, while TNF-alpha amounts progressively increased in a time-dependent fashion. Finally, IL-6 secretion reached peak levels as soon as 18 h of incubation. Taken together, these data point out that monocyte-derived cytokines may play an important role in the immunological control of R. equi infection in immunocompetent people.

Cells, Cultured↗
PubMed1997

Liver inflammation and acute respiratory distress syndrome in a patient receiving hepatitis B vaccine: a possible relationship?

We describe a patient in whom clinical evidence of liver and lung dysfunction developed after he received the second dose of recombinant hepatitis B vaccine, despite no serologic evidence of viral hepatitis. However, liver biopsy specimens demonstrated both surface antigens and core antigens, possibly indicating silent hepatitis B virus infection. A search for an infective etiology for the patient's subsequent clinical deterioration in lung function did not yield pathogens: postmortem examination revealed evidence of immune complex-mediated organ injury in the liver, lungs, and kidneys.

Antigen-Antibody Complex↗
PubMed1997

In-situ immunophenotyping study of hepatic-infiltrating cytotoxic cells in chronic active hepatitis C.

OBJECTIVE: Beside the hypothesis of a direct viral cytopathy, several lines of evidence argue in favour of hepatic damage triggered by immune-mediated mechanisms in hepatitis C virus (HCV) infection. The intrahepatic localization of HCV antigen-specific cytotoxic T-lymphocytes (CTLs) to disease sites has been described; however, very few data are available about the degree and the role of hepatic-infiltrating natural killer (NK) cells in chronically HCV-infected subjects. DESIGN: In a series of percutaneous needle liver biopsies obtained from 35 consecutive untreated patients with chronic active hepatitis C, we performed an in-situ immunophenotyping study to evaluate the degree of cytotoxic NK cell infiltration as compared to CTLs, the hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA-I and HLA-II), and cell adhesion molecules (CAM) in the context of liver inflammatory infiltrates. The data were correlated with the histological activity index (HAI) of disease. RESULTS: In-situ immunophenotyping analysis of CAM provided evidence for the intrahepatic expression of leucocyte adhesion molecules (CD11a and CD2) and their corresponding ligands on hepatocytes (CD54 and CD58) in all cases. A significant parallel expression of CD11a and CD54 as well as CD2 and CD58 structures, restricted to hepatic lobules within the disease sites, was also observed, even if their induction exhibited different degrees of correlation with biological and/or histological activities. A membranous pattern of HLA-I and HLA-II antigen expression on hepatocyte clusters was found in all tissue samples, although HLA-I expression was significantly higher than HLA-II. Moreover, lymphocyte subset analysis displayed a CD8+ T-cell lobular infiltration within inflammatory and/or spotty necrosis areas in all cases, while CD4+ T-cells were confined to the portal and periportal levels. A few scattered CD56+ and CD16+ NK cells, mainly distributed at periportal areas within inflammatory and/or necrotic foci, were detected in 7/35 (20%) and in 5/35 (14.2%) cases, respectively. On the other hand, CD8+ T-cell lobular expression exhibited a linear correlation with HAI (r: 0.698, P < 0.01). Finally, cytotoxic cell infiltration degree did not correlate with HCV serotypes. CONCLUSION: Our findings suggest a limited role for NK cells in the immune mechanism of liver injury in chronic active hepatitis C, while providing further support for the involvement of CD8+ T-cells at disease sites.

Adult↗
PubMed1997

In vitro effects of recombinant human granulocyte-macrophage colony-stimulating factor (RhGM-CSF) on polymorphonuclear cell (PMN) and monocyte (MO) functional capacities in ovarian cancer patients versus human volunteers.

Human polymorphonuclear cells (PMN) and monocytes (MO) from four ovarian cancer patients and seventeen normal donors were in vitro pretreated with different concentrations (25, 50 and 100 IU, respectively) of rhGM-CSF. Phagocytosis and killing of PMN and MO as well as PMN polarization were evaluated in cancer patients before treatment (T0) and at the end of each chemotherapeutic cycle (T1, T2, T3 and T4, respectively) in comparison with normal donors. RhGM-CSF did not affect phagocytosis and killing of PMN and MO. On the other hand, this cytokine was per se endowed with the capacity to enhance PMN polarization in both cancer patients (at T2 interval) and normal donors.

Aged↗
PubMed1997

Role of lipopolysaccharide and related cytokines in Helicobacter pylori infection.

Helicobacter pylori is a gram-negative bacterium which accounts for the development of chronic gastritis and peptic ulcer in man. In this review, emphasis has been laid on the role of lipopolysaccharide (LPS) of the H. pylori cellular wall in the pathogenesis of gastroduodenal disease. H. pylori LPS exhibits a reduced endotoxic potency in terms of pyrogenicity, lethality, toxicity, mitogenicity, cytokine (CK) release and chromogenic limulus amebocyte lysate assay. This low biological activity of the LPS could be ascribed to the underacylation and underphosphorylation pattern of the lipid A backbone. However, also LPS core structures seem to contribute to the biological activity of the molecule. Despite this low immunological potential, an array of proinflammatory CKs are produced both in vitro and in vivo following stimulation of mucosal cells with H. pylori organisms. It is likely that LPS plays a major role in triggering interleukin (IL)-8, IL-1 and tumor necrosis factor-alpha production from both epithelial cells and macrophages. Finally, the lower immune response elicited by H. pylori LPS in comparison with other enterobacterial LPS may represent an escape mechanism from the host immunosurveillance exerted by this bacterium, thus allowing its survival and persistence in the gastric niche.

Animals↗
PubMed1997

CD45RA and CD45RO isoform expression on intrahepatic T-lymphocytes in chronic hepatitis C.

A liver tissue recruitment of antigen-specific cytotoxic cells has been reported in chronic hepatitis C virus (HCV) infection, but whether they really play a role in viral clearance is still a matter of investigation. To further evaluate T-cell involvement in HCV-induced hepatic disease, the authors analysed, in a cohort of chronic hepatitis C patients, the intrahepatic T-cell expression of CD45 isoforms by using specific monoclonal antibodies. Within hepatic specimens, CD45RA+ (naive) cell frequency at the portal tract level was significantly higher than that exhibited at lobular level. At the same time, a large number of CD45RO+ (memory) cells was found at periportal sites in comparison with the lobular counterpart. The evaluation of CD45RA and CD45RO isoform topographical distribution in relation to CD4+ and CD8+ lymphocytes, as determined on serial sections, showed that CD45RA antigen expression was predominantly coexpressed with CD4+ lymphocytes at the portal tract level, and the CD45RO phenotype with CD8 structure at the lobular and periportal sites. The levels of CD45 isoforms did not show any correlation with biological and/or histological disease activities. The results suggest that a liver recruitment of both naive and memory cells occurs during chronic HCV infection, even if their functional role needs to be further clarified.

Adolescent↗
PubMed1996

In vitro effects of 3'-azido-3'-deoxythymidine (AZT) on normal human polymorphonuclear cell and monocyte-macrophage functional capacities.

The in vitro effects of 3'-azido-3'-deoxythymidine (AZT) (at concentrations of 1, 10 and 100 microM, respectively) on normal human polymorphonuclear cell (PMN) and monocyte-macrophage functional capacities were evaluated. Results show that AZT was able to decrease monocyte phagocytosis only, while PMN polarization, phagocytosis and killing were unaffected by drug pretreatment. Quite interestingly, monocyte-derived macrophages maintained their unaltered phagocytic function in spite of the presence of AZT in overnight cultures, thus indicating that monocytes are more susceptible than macrophages to the antiproliferative effects of AZT. Since our data indicate that AZT affects normal human monocyte phagocytosis, it is advisable to evaluate this immune parameter in HIV+ patients administered with this drug.

Adult↗
PubMed1996

Effects of interferon-alpha treatment on neutrophil oxidative metabolism, lymphocyte proliferation and monocyte HLA class I antigen expression in patients with chronic hepatitis C.

Polymorphonuclear cell (PMN) oxidative metabolism, lymphocyte polyclonal proliferation and monocyte HLA class I antigen expression were evaluated at different intervals of time in patients with chronic hepatitis C (CH-C) subjected to a 6 month interferon alpha (IFN-alpha) treatment and divided into Responder ('R') and Nonresponder ('NR') subsets according to clinical outcome. Before therapy, all subjects exhibited multiple immune alterations even if to a different extent between 'R' and 'NR' subsets: an elevated superoxide anion (O2-) generation by suspended PMN, a failure to further increase neutrophil oxidative responsiveness under adherence conditions, an augmented phytohaemagglutin-induced lymphocyte proliferative capacity and an enhanced HLA class I antigen expression on CD14+ cells. IFN-alpha administration gave rise to a modulation of oxidative response in 'R' group only, since these individuals displayed an O2- release by suspended and adherent PMN which fell within normal values. At the same time, a decrease of lymphocyte proliferation occurred in both groups of patients during IFN-alpha therapy, even if it reached statistical significance in 'R' group only. Finally, a more marked difference between 'R' and 'NR' individuals was noted in terms of HLA class I antigen induction on CD14+ cells at the end of therapy, as a consequence of a reduced expression of these structures in 'NR' subjects. Altogether, these findings suggest the occurrence of a strict relationship between immunoresponsiveness and IFN-alpha induced therapeutical effects in CH-C patients.

Adult↗
PubMed1996

Lipopolysaccharide-, granulocyte-monocyte colony stimulating factor and pentoxifylline-mediated effects on formyl-methionyl-leucine-phenylalanine-stimulated neutrophil respiratory burst in the elderly.

The impairment of superoxide anion (O2-) generation by aged polymorphonuclear cells (PMN) stimulated with formyl-methionyl-leucine-phenylalanine (FMLP) has been reported. In this work the effect of lipopolysaccharide (LPS), granulocyte-macrophage colony stimulating factor (GM-CSF) and pentoxifylline (POF) pretreatment on FMLP-triggered neutrophil oxidative metabolism in a group of healthy elderly individuals, was investigated. Results provide evidence that LPS and/or GM-CSF priming was able to enhance O2- production in old PMN, even if values were still lower than those observed in similarly-treated young cells. Moreover, even if the lag period was unaffected by inflammatory mediator treatment, the priming gave rise to a significant increase of maximum O2- release rate. On the contrary, POF pretreatment led to a significant decrease of oxidative responsiveness in either unprimed or primed PMN suspensions. These findings suggest the occurrence of different mechanisms in the imbalance of FMLP-activated neutrophil oxidative responsiveness during senescence. This may be of paramount significance for explaining the augmented frequency of severe infectious diseases with advancing age.

Aged↗
PubMed1996

Hepatitis C virus infection. Biological and immunological features.

The recent cloning and genomic identification of hepatitis C virus (HCV) by sensitive and specific immune techniques has allowed a better definition of both histopathological and clinical features of the previously not well defined non-A, non-B hepatitis. In this regard, antibodies to different HCV antigens are usually found during infection, even if some of them such as anti-E1 and anti-E2/NS1 have been shown to be associated with significant viraemic levels. Acute hepatitis C is self-limiting in a minority of cases only. Over 60% of acute hepatitis becomes in fact chronic and may progress towards cirrhosis. In about 10% of cases, hepatocellular carcinoma may develop in cirrhotic livers. The occurrence of a strict relationship between immunoresponsiveness and disease activity is suggested by the observation that peripheral blood mononuclear cell (PBMC) proliferation induced by NS3 structure is associated with self-limiting acute hepatitis, while PBMC stimulation by core antigen characterizes chronic C hepatitis. The demonstration of lymphoid aggregates, bile duct lesions, intraportal lymphocyte infiltration, increased adhesion molecule expression and augmented cytokine release clearly emphasizes the involvement of immune-mediated reactions in the development of liver damage, even if a direct cytopathic effect cannot be excluded. Finally, it is likely that HCV may favour, through immune-mediated mechanisms, autoantibody generation and/or the appearance of some extrahepatic autoimmune manifestations during the course of HCV chronic infection.

Animals↗
PubMed1996

Neutrophil activation in nickel sensitized subjects.

Conflicting results were obtained from the evaluation of nickel-mediated effects on immunoresponsiveness. A reduction of B cell polyclonal response, mixed lymphocyte reaction, T lymphocyte proliferation and natural killer cytotoxicity was evident following nickel salt exposure. On the contrary, an enhancement of cytokine release, T cell proliferative capacity and adhesion molecule expression was found in nickel sensitized donors. In addition, under different experimental conditions, respiratory burst induction and myeloperoxidase release by polymorphonuclear cells (PMN) in a group of individuals exhibiting nickel hypersensitivity were investigated. Results provide evidence that nickel allergic individuals displayed a significant increase of superoxide anion (O2-) generation by suspended PMN in comparison with similar cell suspensions from healthy donors, but this was not the case when adherent neutrophils were used as effector cells. PMN from nickel sensitized donors exhibited a significant enhancement of hydrogen peroxide (H2O2) and myeloperoxidase release. The results imply the occurrence of neutrophil activation in nickel hypersensitivity, which in turn may be responsible for the low frequency of life-threatening infections in these subjects.

Adult↗
PubMed1995

Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact: a possible role for membrane-associated interleukin-6 and interleukin-8.

Polymorphs (PMN) and monocytes/macrophages (Mo) play a very important role in the host defence since they participate to inflammatory processes, tissue repairing and antitumor activity. Previous studies showed that lipopolysaccharide (LPS)-activated Mo are able to upregulate PMN phagocytic ability via cell-to-cell contact mechanisms mediated by bound to Mo membrane (m) cytokines (CKs), such as Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-1 alpha and IL-1 beta. Based on these grounds, the role of Mo m-associated IL-6 and IL-8 on the modulation of PMN activity has been evaluated. In the first step, PMN incubated with lipid A (LA)-activated Mo showed an increased phagocytosis dependent on cell-to-cell contact only. In the second step, LA-activated Mo were pretreated with antirecombinant human (Rhu) IL-6 and IL-8 monoclonal antibodies (MoAbs), respectively and, in such a way, the enhanced phagocytic activity of PMN was abrogated. In the third step, PMN incubated with LA-activated supernatants (AS) from PBMC cultures exhibited an enhanced phagocytic activity, that was abrogated when LA-AS were pretreated with anti-Rhu IL-6 and anti-Rhu IL-8 MoAbs, respectively. These data suggest that IL-6 and IL-8 associated to Mo membrane may modulate PMN activation through a cell-to-cell contact dependent pathway.

Adult↗
PubMed1995

Role of lymphocyte function-associated antigen-1 on the interplay between lipid A-activated monocytes and polymorphonuclear cells.

Previous findings provided evidence that bacterial lipopolysaccharide (LPS)-activated human monocytes are able to upregulate autologous polymorphonuclear (PMN) phagocytic ability via cell-to-cell contact mechanisms mediated by membrane (m)-associated cytokines (CKs), such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6 and IL-8. Consequently, the role of the lymphocyte function-associated antigen (LFA)-1 molecule on the monocyte (Mo)-PMN interplay was evaluated. In the first step, lipid A (LA)-stimulated Mo were pretreated with anti-recombinant human (Rhu) LFA-1 alpha monoclonal antibody (MoAb), and the enhanced phagocytic activity of PMN was abrogated. Pretreatment of unstimulated Mo with the same MoAb led to a reduction of PMN phagocytosis. In the second step, the role of m-LFA-1 on PMN was investigated with regard to Mo modulation. Anti-Rhu LFA-1 alpha MoAb was supplemented to LA-activated and unstimulated PMN, respectively, before coculturing with autologous LA-activated Mo. The addition of anti-Rhu LFA-1 alpha MoAb gave rise to a significant decrease in PMN phagocytosis regardless of PMN activation. These data suggest that, besides m-CKs, LFA-1 present on Mo and PMN might be involved in the mutual interplay between PMN and Mo.

Antibodies, Monoclonal↗
PubMed1995

Effects of in vitro nutrient supplementation on polymorphonuclear cell respiratory burst in primary IgA nephropathy.

Since recent findings have pointed out a key role for reactive oxygen species in kidney diseases, we investigated superoxide anion (O2-) and hydrogen peroxide (H2O2) generation by peripheral blood polymorphonuclear cells (PMN) in 20 patients with primary IgA nephropathy (IgAN). Results provided evidence for a significant enhancement of O2- and H2O2 production in IgAN subjects in comparison to patients affected by hypertensive renal injury and healthy donors. Among the IgAN group, the highest oxidative metabolism was observed in patients with severe histologic lesions. On the other hand, in vitro vitamin and/or trace element supplementation to PMN suspensions led to a down modulation of their oxidative responsiveness. These data were further supported by the assessment of O2- release on a kinetic basis. Nutrient pretreatment was in fact able to antagonize either the IgAN-related shortening of the lag period or the increase of maximum O2- production rate following agonist stimulation. Taken together, these findings indicate that an exaggerated PMN oxidative metabolism occurs in IgAN and suggest a potential role for micronutrients in the modulation of PMN metabolic pathway.

Adolescent↗
PubMed1994

Age-associated changes of neutrophil responsiveness in a human healthy elderly population.

Conflicting results have been reported on polymorphonuclear (PMN) cell responsiveness during senescence. Consequently, neutrophil absolute numbers and PMN-mediated chemotaxis, phagocytosis, killing and superoxide anion (O2-) generation in healthy aged volunteers divided into different groups according to increasing age criteria, were investigated and evaluated. Data provide evidence that absolute amounts of PMN cells declined in a significant manner in donors over 85 years old only when compared with young subjects. On the contrary, regardless of age, the aged individuals exhibited a significant impairment of PMN chemotactic, phagocytic and killing functional capacities. Finally, formyl-methionyl-leucyl-phenylanaline (FMLP)-triggered O2- release was reduced in all elderly groups, while depression of O2- production was seen in subjects between the age of 86 and 104 years using phorbol 12-myristate 13-acetate (PMA) as agonist. These findings indicate that an imbalance in the PMN cell immune reactivity occurs throughout the senescence process.

Adult↗
PubMed1994

Modulation of pokeweed mitogen-induced B cell differentiation by polymorphonuclear cells: effects of bacterial lipopolysaccharides.

The capacity of polymorphonuclear (PMN) cells to release several cytokines stresses the potential immunomodulatory role of these cells. The effects mediated by purified PMN cell suspensions on pokeweed mitogen (PWM)-driven B cell differentiation was investigated. Results showed that the addition of increasing concentrations of resting PMN cells to peripheral blood mononuclear cell (PBMC) cultures gave rise to inhibition of immunoglobulin (Ig) production. At the same time, similar results were obtained using lipopolysaccharide (LPS)-pretreated PMN cells. In contrast, when LPS, at different concentrations, and PMN cells were both added to PBMC cultures an enhancement of IgG or IgM release in comparison with cultures treated with PMN cells only occurred at low PMN cell/PBMC ratios (1:20 and 1:10), which was maximal in the presence of 10 or 100 ng/ml LPS. This effect was probably mediated by LPS-induced monocyte stimulation, since the supplementation of LPS-activated monocyte supernatants to PMN cell/PBMC cocultures led to an Ig synthesis which mimicked that seen in similarly-treated PBMC cultures. These data suggest the occurrence of various in vitro modulatory effects in the interactions between PMN, LPS and lymphocytes in a PWM-induced B cell polyclonal responsiveness system.

B-Lymphocytes↗