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Biomedical subjects

S Antonaci

Publications and source records attributed to S Antonaci.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Evaluation of phagocyte functions, inflammatory lymphokine activities and in vitro antibody synthesis in patients with active and chronic pulmonary tuberculosis.

In fourteen patients with pulmonary tuberculosis (TBC) (seven active and seven chronic cases) non-specific immunity and B cell function were evaluated. Polymorphonuclear cell (PMN) and monocyte chemotaxis, phagocytosis and killing were depressed to a different extent regardless of the disease status. Additionally, determination of lymphocyte-derived chemotactic factor and leukocyte inhibitory factor activities indicated a reduced production of these two lymphokines. This may also explain the impairment of phagocyte functions. Furthermore, the frequency of T cell subsets was slightly modified except for the increased number of CD25+ cells. The in vitro antibody response was analysed in a plaque-forming cell system using pokeweed mitogen (PWM) as a polyclonal activator and purified protein derivative (PPD) as a specific antigen. Results show that in patients with active TBC the anti-PPD antibody response was markedly enhanced, while in both groups of patients PWM-induced antibody synthesis was normal. These findings indicate several immune deficiencies related to phase activity which occur during the course of the disease.

Adult↗
PubMed1991

HIV-infection and in vivo lipopolysaccharide-induced release of cytokines. An amplified mechanism of damage to the host.

Bacterial lipopolysaccharides (LPS) or endotoxins are potent triggers of the cytokine (CK) cascade. These CKs are immune mediators which produce many biological effects and could play a detrimental rather than beneficial role in the host. In this review emphasis will be placed on the participation of two CKs, tumor necrosis factor [TNF-alpha and interleukin (IL-1) beta], in the pathogenetic development of HIV infection. We have found that TNF and IL-1 circulate in exaggerated amounts in the blood of HIV-infected subjects from the earliest phases of infection. Furthermore, we have observed a strict correlation between plasma LPS and IL-1 beta levels, thus indicating that endotoxins could account for the production of CKs in the course of HIV infection. Finally, the demyelinating role of TNF-alpha either in experimental models or in the course of AIDS dementia complex is outlined.

Animals↗
PubMed1990

Senile dementia, Alzheimer type: a distinct entity in the immunosenescence?

Since previous data have provided conflicting results on immunoresponsiveness in senile dementia, Alzheimer type (SDAT), we evaluated the immune function in groups of SDAT patients and aged and young donors. In comparison to the younger subjects, SDAT and aged subjects did not exhibit significant differences in lymphocyte surface markers. Both groups of aged donors showed decreased B cell polyclonal responsiveness in a nonspecific T cell-driven B lymphocyte differentiation system. The use of an antigen-specific induction assay revealed an imbalance of T helper (Th) or T suppressor function in the elderly, while SDAT individuals were characterized by decreased Th activity. At the same time, aged individuals manifested an impairment of leukocyte-inhibiting factor (LIF) and lymphocyte-derived chemotactic factor production; a selective deficit of LIF release was seen in SDAT. Finally, elderly individuals displayed a decline of polymorphonuclear cell (PMN)-mediated functions and monocyte phagocytosis; only a decrease in PMN response was observed in SDAT. These results reveal discrepancies in impaired immune responses between SDAT and aging.

Adult↗
PubMed1990

Report of the symposium on the use of intravenous gammaglobulin in adults infected with the human immunodeficiency virus.

On July 27, 1989, the International Conference on Molecular Aspects of Immune Response and Infectious Diseases devoted a symposium to the subject of the use of intravenous gamma globulin (IVIG) in acquired immunodeficiency syndrome (AIDS). The information presented confirmed that IVIG benefits human immunodeficiency virus (HIV)-infected children with recurrent infections and that much remains to be learned about the influence of IVIG in adult AIDS. The symposium participants recognized the urgent need to develop randomized clinical trials using a control group to assess the efficacy of a treatment with IVIG in PGL (persistent generalized lymphadenopathy), ARC (AIDS-related complex), and AIDS. To prepare this report, a committee was established, including individuals with expertise in immunology, immunopharmacology, microbiology, virology, infectious diseases, general medicine, and pediatrics and representing research experience in academia and hospitals. After an introduction to the report with a summary of immunotherapeutic agents under evaluation to treat HIV infection, section 1 lays out the present understanding of the disease pathogenesis. Section 2 then outlines the treatment of HIV-seropositive individuals, discussing the uncertainties that any treatment entails. Section 3 discusses the rationale for treating HIV-infected individuals with IVIG, and Section 4 examines the major differences between IVIG and hyperimmunoglobulins for the treatment of HIV infection. Section 5 looks at IVIG as a mean to delay the emergence of opportunistic infections and restore immunocompetence in AIDS and related illnesses, and Sections 6 and 7 suggest a pilot protocol on the use of IVIG in association with low-dose or standard-dose zidovudine (AZT).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Role of bacterial lipopolysaccharides in the development of natural antibacterial activity mediated by human peripheral blood T lymphocytes.

The role of bacterial lipopolysaccharides (LPS) has been evaluated for their influence on the human T cell-mediated anti-Salmonella typhi activity. In nonendemic areas for salmonellosis this activity is exerted by CD4+ lymphocytes armed by IgA, whereas in endemic zones besides these cells also CD8+ lymphocytes armed by IgG display an elevated anti bacterial activity. These results suggest that, in endemic regions, continuous antigenic challenge and, in particular, that exerted by lipid A (the active moiety of LPS) may play a role in triggering this activity. In other series of experiments, pretreatment of endemic peripheral blood lymphocytes (PBL) with smooth and rough (Rb and Re) forms of Salmonella LPS leads to the inhibition of antibacterial activity. In this respect, Re-LPS, which contains lipid A covalently linked to the core-chetodeoxyoctonate, gives rise to the maximum of inhibition. Finally, fractionation of PBL by means of S. minnesota R345 (Rb) cytoadherence has led to the conclusion that anti bacterial activity is present in the Rb-unbound population, thus indicating that bacterial adherence to PBL is a distinct phenomenon from natural anti-S. typhi activity. The overall results suggest that lipid A is able to modulate the expression of antibacterial activity exerted by human peripheral blood T cells.

Adult↗
PubMed1990

Serum suppressive factors may account for the reduced polymorphonuclear cell function in haemophilia.

Haemophiliacs exhibit a broad range of immune defects. In this regard we have investigated the functional capacity of purified polymorphonuclear (PMN) cell suspensions in a group of Human Immunodeficiency Virus (HIV)+ or HIV- patients. Our results provide evidence for a significant reduction of PMN-mediated chemotactic responsiveness, phagocytosis and killing in haemophiliacs regardless of HIV infection. The depressed response does not reflect a PMN intrinsic dysfunction, since respiratory burst activity and lysosomal enzyme release from haemophilic PMN are unaffected in comparison to healthy donors. Quite interestingly the pretreatment of PMN from normal donors with either HIV+ or HIV- haemophilic sera gives rise to a reduction of PMN activity. Moreover, the suppressive effect is abrogated by serum heat inactivation. Taken together, these findings indicate a role for serum suppressive factors in the imbalance of PMN functional capacity in haemophilia regardless of HIV infection.

Adolescent↗
PubMed1989

Effects of substance P on the spontaneous binding of Salmonella minnesota R345 (Rb) to human peripheral blood lymphocytes.

The effects of substance P (SP) on Salmonella minnesota R345 (Rb) binding to human peripheral blood lymphocytes (PBL) were evaluated. Two parameters of bacterial cytoadherence were considered, namely the binding lymphocytes (BL) and the number of bound-bacteria/lymphocyte (BB). The results showed that SP inhibits both BL and BB in a significant manner. Furthermore, distribution of Salmonella binding to CD4+ and CD8+ lymphocytes was studied following SP pretreatment of lymphoid cells. This neuropeptide is able to hamper the bacterial cytoadherence to both T-cell subpopulations and, in particular, the inhibitory effect on the T-suppressor/cytotoxic subset was more pronounced. These findings are discussed in terms of SP intervention in the mechanism of host protection against invading microorganisms.

Antigens, CD↗
PubMed1989

Monocyte- and cytokine-mediated effects on T immunoregulatory activity in the elderly.

Aged individuals exhibit an impairment of T helper and/or T suppressor activity on B cell function in an antibody-specific induction system. Further evidence is now provided that soluble suppressive factors acting on monocytes play a key role in such deficits. In fact, overnight preincubation of isolated monocytes and supplementation of autologous lymphocytes reverses the immunoregulatory imbalance. The suppressive factors are also responsible for a decreased interleukin 2 (IL-2) synthesis since a similar pretreatment of cell suspensions or exogenous human IL-1 and/or IL-2 supplementation of aged cell cultures leads to a recovery of T regulatory effects on B cell differentiation. Similar effects are observed in the presence of thymopentin, a well known IL-2 inducer. Interferon alpha and gamma addition to cultures gives rise to a restoration of T immunoregulatory effects. These findings suggest that several mechanisms are involved in the depressed T immunoregulatory activity in the elderly.

Aged↗
PubMed1989

Imbalance of T cell immunoregulatory subsets in primary IgA nephropathy.

The peripheral blood distribution of T cell subsets was evaluated in a group of patients with primary IgA nephropathy (IgAN). Results showed that the frequency of helper (CD4+) and suppressor (CD8+) T lymphocytes in IgAN overlapped that seen in healthy blood donors. In addition, the helper T cell subset (CD4+ CDW29+ and CD4+ CD45R+ cells, respectively) proportion was normal, while with particular reference to suppressor T cell subpopulations, a significant decrease of CD8+ CD11+ lymphocytes (the true suppressor cells) was observed in IgAN. These data were further confirmed by the demonstration that monocyte chemotactic responsiveness triggered by lymphocyte-derived chemotactic factor (LDCF), a lymphokine released by CD8+ CD11- cells, was higher in IgAN than in controls. These data suggest that the low frequency of CD8+ CD11+ cells may be responsible for the impaired T cell immunoregulatory activity in patients with IgAN.

Adult↗