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Biomedical subjects

S Antonaci

Publications and source records attributed to S Antonaci.

At least 19 recordsLinked to original sources
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↗
PubMed1994

In vitro vitamin E and selenium supplementation improves neutrophil-mediated functions and monocyte chemoattractant protein-1 production in the elderly.

The in vitro effects of vitamin E and selenium on either polymorphonuclear cell (PMN)-mediated chemotaxis and phagocytosis or monocyte chemoattractant protein-1 (MCP-1) production in 21 well-nourished elderly donors were evaluated. Results show that, before treatment, old subjects were characterized by a decrease of both PMN functions and cytokine (CK) release. By contrast, in vitro vitamin E and selenium supplementation was able to enhance significantly the depressed PMN activities and MCP-1 synthesis. These findings suggest a role for both nutrients in the modulation of impaired phagocyte responsiveness during senescence.

Aged↗
PubMed1993

Relationship between respiratory burst and adhesiveness capacity in elderly polymorphonuclear cells.

Polymorphonuclear cell (PMN) activation was assessed in 30 aged donors, in terms of either adherence to different substrates or superoxide anion (O2-) generation by adhering and suspended cells in response to several agonists. Results showed that PMN in suspension from elderly individuals displayed a phorbol 12-myristate 13-acetate (PMA)-triggered O2- responsiveness which overlapped that seen in the younger counterpart, while a significant decrease of respiratory burst was observed in the presence of formyl-methionyl-leucine-phenylalanine (FMLP). Moreover, in spite of a normal nylon fiber adhesiveness, aged individuals exhibited a reduced PMN adherence to foetal calf serum (FCS)-coated plastic surfaces by using either PMA or FMLP as stimulant. However, elderly adhering cells produced higher amounts of O2- than homologous neutrophils in suspension. Cell pretreatment with anti-CD11b, anti-CD11c and anti-CD18 antibodies led to a further inhibition of PMN adhesion to FCS-coated plates. By contrast, under the same experimental conditions, O2- generation from adhering cells was reduced by using anti-CD18 antibody only. Altogether, these findings provide additional evidence for an imbalance of PMN-mediated functions in the elderly.

Adult↗
PubMed1993

Supplementation of male inhibitory material to lipid A activated human mononuclear cell supernatants contributes to the suppression of polymorphonuclear cell phagocytosis.

Human normal peripheral blood mononuclear cells were stimulated with lipid A (LA), the biologically active moiety of bacterial lipopolysaccharides. LA-activated supernatants were able to suppress polymorphonuclear cell (PMN) phagocytosis of Candida albicans. This inhibitory activity was enhanced by the supplementation of male inhibitory material (MIM) to active supernatants. The addition of a recombinant human anti-interleukin-1 beta monoclonal antibody to activated supernatants in the absence or presence of MIM diminished or abrogated, respectively, the suppressive effect on PMN function. The mechanisms and the significance of MIM-mediated inhibition of phagocytosis under these circumstances are discussed.

Adult↗
PubMed1993

Polymorphonuclear cell-mediated phagocytosis and superoxide anion release in insulin-dependent diabetes mellitus.

It is well known that patients with insulin-dependent (or type I) diabetes mellitus are at high risk for bacterial infections. Since conflicting results have been reported on non-specific immune responses in type I diabetes, polymorphonuclear cell (PMN)-mediated phagocytosis and superoxide anion (O2-) generation in a group of individuals with well-controlled type I diabetes mellitus were assessed. Results showed that diabetic subjects were characterized by a significant impairment of phagocytic capacity when compared with healthy donors, while O2- release mimicked that seen in controls. Cell pretreatment with beta-hydroxybutyric acid (beta-HB) gave rise to a significant reduction in either phagocytosis or O2- production by PMN from type I diabetic individuals. Finally, beta-HB and glucose mixture supplementation to PMN suspensions did not induce any modification of their functional activities in comparison with those exerted by cells treated with beta-HB only. A disease-related or beta-HB-mediated PMN dysfunction in insulin-dependent diabetes mellitus is indicated.

3-Hydroxybutyric Acid↗
PubMed1992

Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact. A possible role for membrane-associated cytokines.

Previous findings have shown that lipopolysaccharide (LPS)-activated human monocytes express cytokines (CKs) on their membrane. Furthermore, those associated to membrane products such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 have been demonstrated to exert many biological activities. In this paper, evidence is provided that human polymorphonuclear cells (PMN) exhibited an increased phagocytic capacity following incubation with either lipid A (LA)-activated autologous monocytes or supernatants recovered from LA-stimulated mononuclear cell cultures. In order to investigate the possible role of monocyte membrane-associated TNF-alpha, IL-1 alpha and IL-1 beta in the modulation of PMN activity, in a separate series of experiments LA-activated monocytes or LA-activated supernatants were pretreated with anti-recombinant human (Rhu) TNF alpha, anti-Rhu IL-1 alpha and anti-Rhu IL-1 beta monoclonal antibodies (MoAbs), respectively. Such an approach gave rise to an abrogation of monocyte-mediated triggering effect on PMN functional capacity. Taken together, these data suggest that activated monocytes can upregulate PMN phagocytosis by a cell-to-cell contact mechanism, likely related to membrane-associated CKs.

Antibodies, Monoclonal↗
PubMed1992

Thymostimulin administration modulates polymorph metabolic pathway in patients with chronic obstructive pulmonary disease.

Several studies outline the imbalance of phagocyte functions in chronic obstructive pulmonary disease (COPD). In this regard, here, we have assessed either monocyte- and polymorphonuclear cell (PMN)-mediated chemotactic, phagocytic and killing capacities or PMN-triggered metabolic pathway in a group of COPD patients before and at different times after thymostimulin administration. Before therapy, an increase of O2-generation and a decrease of myeloperoxidase release were found in these individuals when compared to controls. Moreover, a reduction of either PMN-mediated chemotaxis and killing or monocyte chemotactic capacities was observed. By contrast, no differences were seen in terms of beta-glucuronidase release, monocyte-mediated killing and PMN or monocyte phagocytic function. During a one-year monitoring following immunotherapy, O2- production and myeloperoxidase activity fell within normal values, while phagocyte functional capacities were unaffected by such a treatment. Furthermore, COPD subjects exhibited a significant improvement of their clinical status as assessed during a one-year followup. All together, these findings suggest a potential role for thymostimulin in the treatment of COPD patients.

Adjuvants, Immunologic↗
PubMed1992

Redistribution of natural killer (NK) cell frequency and NK cytotoxic activity in primary IgA nephropathy.

Recent findings have indicated an imbalance of immune responsiveness in primary IgA nephropathy (IgAN). Thus natural killer (NK) cell frequency and NK cytotoxicity were evaluated in fifteen IgAN patients. CD8+, CD11+, CD56+ and CD57+ lymphocyte percentages in IgAN individuals fell within normal values, while a significant decrease of CD16+ cells was observed in the same group of patients. In contrast, NK activity overlapped that seen in controls as assessed by an agarose-single cell cytotoxic assay. To further investigate the discrepancy between CD16+ cell level and NK cytotoxic activity in IgAN, the proportion of CD11+ CD57+, CD56+ CD16+ and CD57+ CD16+ lymphocytes was determined. In spite of the unaffected CD56+ CD16+ cell frequency, IgAN subjects exhibited a significant decrease of CD11+ CD57+ and CD57+ CD16+ lymphocyte percentages in comparison to controls. It is suggested that a redistribution of NK lymphocyte subsets occurs in IgAN. This may have an important role in the impairment of the immunoregulatory network.

Adult↗
PubMed1992

Role of interleukin 2, interleukin 4 and interleukin 5 in the T helper cell-driven B cell polyclonal differentiation in the elderly.

There is evidence for an impaired T cell-mediated B cell response during senescence. In thirty aged donors, pokeweed mitogen (PWM)-driven immunoglobulin (Ig) synthesis by B cells co-cultured with autologous enriched CD4+ lymphocytes and low amounts of monocytes, was evaluated. Under such experimental conditions, elderly cultures displayed a reduced IgG and/or IgM production when compared with the younger counterpart. Moreover, interleukin (IL)-2 and/or IL-5 addition to cultures led to an enhancement of Ig release. In contrast, IL-4 supplementation failed to positively modulate B cell differentiation. At the same time, aged cells cultured in the presence of IL-2 + IL-5 exhibited an increased Ig synthesis, while the addition of IL-2 + IL-4 or IL-4 + IL-5 mixtures did not induce any significant effect in comparison with homologous untreated samples. The results suggest a critical role for IL-2, IL-4 and IL-5 in the modulation of T helper cell-driven B cell polyclonal responsiveness in the elderly.

Aged↗
PubMed1992

[The role of free oxygen radicals in myocardial damage from ischemia/reperfusion, in chronic obstructive bronchopneumopathy and in aging].

During the last few years, several observations point out that oxygen-free radicals may play a pivotal role in the development of myocardial ischaemic/reperfusion injury, chronic obstructive pulmonary disease (COPD) and aging. With particular reference to acute myocardial ischaemic syndrome, these compounds may account for reperfusion-mediated ventricular arrhythmias, myocardial stunning and cell death. Such molecules may also be involved in lung damage during the course of COPD. In this regard, polymorphonuclear cell (PMN) recruitment at myocardial and/or lung level play an important role in oxygen-free radical overproduction. Several factors may, in fact, trigger PMN adhesion, respiratory burst and/or lysosomal enzyme release, this leading to a deleterious effect for the host. As far as elderly is concerned, evidence has been provided for a strict relationship between oxygen-free radical generation and metabolic rate. Nevertheless, the occurrence of PMN impaired functions and malnutrition in aged subjects gives rise to an enhanced synthesis of these compounds. All together, these findings outline the toxicity of oxygen-derived radicals and suggest the usefulness of a therapeutical approach to antagonize their effects.

Aging↗
PubMed1991

Human melanoma metastasis culture supernatant contains chemotactic factors for phagocytes.

Several findings point out that melanoma culture supernatants release soluble factors which modulate mononuclear cell chemotactic responsiveness. In this regard, either an enhancement or an impairment of chemotactic capacity has been found. Here, we provide evidence that supernatant recovered from human melanoma cell metastasis culture is able to trigger monocyte and polymorphonuclear cell chemotaxis. This activity is not affected by the presence of anti-IL-1 antibody during the assay. Further studies are in progress to isolate and characterize soluble factors involved in this activity.

Chemotactic Factors↗
PubMed1991

Modulating effects on CD25 and CD71 antigen expression by lectin-stimulated T lymphocytes in the elderly.

During the last few years, several observations outline that the impaired T lymphocyte proliferative capacity in the elderly is due to a reduced interleukin 2 (IL-2) release. To further investigate the activation process during lectin stimulation, aged peripheral blood mononuclear cells (PBMC) were stimulated with phytohemagglutinin (PHA) and assessed for CD25 (IL-2 receptor) and CD71 (transferrin receptor) expression at different intervals of time. Our results provided evidence for a significant decline of both structure induction, above all in the later phase of culture. Indomethacin (INDO) treatment gave rise to an enhancement of CD71 antigen expression only, while prostaglandin E2 (PGE2) supplementation to culture media further decreased either CD25 or CD71 receptor induction. Interferon (IFN)-alpha and IFN-gamma treatment failed to modulate the frequency of CD25+ and/or CD71+ cells. Finally, the expression of CD71 receptor was increased by deferoxamine supplementation, this suggesting a partial involvement of iron overload in the depressed function. Although further studies are required to evaluate at a molecular level the decreased antigen expression, these findings indicate that several mechanism are involved in the elderly-related decline of T lymphocyte activation structures during lectin stimulation.

Aged↗