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Biomedical subjects

S Antonaci

Publications and source records attributed to S Antonaci.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1989

Cell-mediated immune response in psoriasis and psoriatic arthritis.

It has been previously described an impairment of cell-mediated immune response in psoriasis. In the present paper we have evaluated lymphocyte surface markers, non specific immunity, lymphokine secretion and antibody synthesis in a group of patients with psoriasis (PS) and with anti-inflammatory drug treated or gold-treated psoriatic arthritis (PsA). No significant differences are found in terms of T lymphocyte subpopulation frequency, even if a lower CD8+/CD4+ ratio was observed in all patients. In spite of an increased percentage of B lymphocytes, B cell polyclonal response is significantly decreased in the presence of either T cell-independent or T cell-dependent polyclonal activator. Further studies provide additional supports to these findings, since all psoriatic patients exhibit a deficit of T helper function in an antibody-specific induction system. Gold therapy in PsA led to a partial recovery of T helper function, without affecting the immunoglobulin reduced synthesis. With particular reference to non-specific activities mediated by monocytes and polymorphs (PMN), PMN chemotaxis, phagocytosis and killing and monocyte-mediated phagocytosis are reduced, except for monocyte phagocytosis in anti-inflammatory treated PsA or PMN chemotaxis in gold-treated PsA. Finally, lymphokine release is significantly decreased in all patients. In conclusion, our data provide further evidence for the impairment of immune response in psoriasis and PsA, which may in turn play a key role in the pathogenesis of psoriasis.

Adult↗
PubMed1988

Inhibition of lymphocyte-mediated antibacterial activity by human seminal plasma.

Seminal plasma displays a suppressive function on many immunological responses. In light of recent findings on the antibacterial activity mediated by different lymphocyte subsets, we have assessed the effect of male inhibitory material (MIM) in this system. Results provide evidence that MIM pretreatment of peripheral blood lymphocytes (PBL) leads to a significant inhibition of antibacterial activity against Salmonella typhi and S. minnesota R345 (Rb). Both CD4+ and CD8+ cell-mediated activities are reduced by this treatment, while another defense mechanism (bacterial binding to PBL) is unaffected. Taken together, these results indicate a role for MIM in the depression of immune response and suggest that lymphocytes mediating antibacterial activity and bacterial cytoadherence are different entities.

Blood Bactericidal Activity↗
PubMed1988

Interactions of lymphocytes with bacterial antigens.

Several observations indicate that smooth (S) and rough (R) Salmonella strains display the capacity to spontaneously adhere to lymphoid cell membrane. Such a phenomenon is confined to T lymphocytes and affects both CD4+ and CD8+ cells. As far as receptor structures on lymphocytes surface are concerned, the lipopolysaccharides (LPS) of the bacterial cell wall play a key role in human and murine cytoadherence. In addition, evidence has been provided that LPS of gut flora induce bacterial binding as assessed by the evaluation of cyto-adherence at different anatomical sites. Interestingly, cells mediating nonspecific immune responses are not involved in the bacterial binding, since the unbound fraction is highly enriched for cytotoxic and T helper cells. The in vivo occurrence of binding in typhoid fever patients suggests that this activity may represent an earlier event during the course of infection. These findings are also supported by the demonstration that chemotherapeutic treatment abolished bacterial binding in both vitro and in vivo systems. Finally, the production of lymphokines following bacterial stimulation points out the importance of bacterial/immune system interaction in the development of immune response during gram-negative sepsis.

Antigens, Bacterial↗
PubMed1988

Immunoresponsiveness in hemophilia: lymphocyte- and phagocyte-mediated functions.

Several deficits of immune response have been reported in hemophiliacs. In order to evaluate the overall immune function in this disease, we have investigated peripheral blood mononuclear cells (PBMC) surface phenotype, lymphokine production, B cell responsiveness, monocyte- and polymorphonuclear (PMN) cell-mediated responses in a group of 25 A or B hemophiliac patients. They were treated with concentrates (greater than 30,000 U/year) for at least 8 years, and ten of them were positive for human immunodeficiency virus (HIV) infection. With particular reference to lymphocyte surface markers, a low CD4+/CD8+ ratio and an increased frequency of CD25+ and surface immunoglobulin (sIg) positive lymphocytes were noted in HIV+ subjects. By contrast, CD3+ and CD4+ cell frequency was decreased in HIV- patients, whereas in the same individuals CD11+ and sIg+ cell percentage was augmented. Regardless of HIV infection, a quite variable degree of B-cell response was seen in hemophiliacs with either a T-independent or a T-dependent polyclonal B cell activator. PMN chemotaxis, phagocytosis, and killing were significantly diminished, whereas similar monocyte functions were basically unaffected. Finally, hemophiliacs were characterized by a profound impairment of leukocyte inhibiting factor (LIF) and lymphocyte-derived chemotactic factor (LDCF) production. Our findings clearly indicate an impairment of immune function in hemophiliacs regardless of HIV infection.

Adolescent↗
PubMed1988

Cell-mediated immune response in patients with type IIa, type IIb and type IV primary hyperlipoproteinaemia.

Plasma lipoproteins inhibit immune function. Polymorphonuclear cell (PMN) and monocyte activities, and pokeweed mitogen (PWM)-driven B cell differentiation in patients with type IIa, type IIb and type IV primary hyperlipoproteinaemia were evaluated. Evidence is provided for a selective impairment of these functional capacities in type IIa and type IIb hyperlipoproteinaemic patients, while immune responsiveness is unaffected in type IV primary hyperlipoproteinaemia. The data suggest a specific immune dysfunction in patients with type IIa and type IIb primary hyperlipoproteinaemia.

Adult↗
PubMed1987

Pilot study of intravenous administration of the acid-treated Salmonella minnesota R595 (Re) in cancer patients.

The clinical toxicity of acetic acid-treated "Salmonella minnesota" R595 (Re) organisms was evaluated in 24 cancer patients. Bacteria were injected i.v. four times at increasing doses for a total of 6.5 micrograms. This therapeutic regimen was free of major side effects (one patient had fever higher than 38 degrees C and 10 patients complained of pruritus). Furthermore, this bacterial preparation which possesses a more exposed lipid A on its surface, exhibited immunomodulating capacities in that it normalized the inverted T helper/T suppressor ratio and enhanced natural killer activity in tumor patients. The mechanisms of the lower toxicity and immunomodulating activities of these bacteria compared to other lipid A preparations are discussed.

Acetates↗
PubMed1987

Regulatory effects mediated by OKT8+ subsets on B cell response in the elderly.

The B cell responsiveness mediated by T cells has been evaluated in 50 aged donors by using a Pokeweed mitogen (PWM)-driven differentiation system. Peripheral blood mononuclear cells (PBMC) from aged donors exhibited a lower plaque-forming cell (PFC) generation in comparison with young donors. Similar results were obtained by using, on a per cell basis, purified T cells supplemented with Non-T lymphocytes. OKT4+ cell addition to Non-T cells enhanced PFC number, even if values were still lower when compared to young donors. Moreover, results similar to those seen with T-supplemented Non-T cell cultures were obtained by mixing Non-T cells with OKT4+ and OKT8+ lymphocytes. Interestingly, when OKT8+ cells were divided into OKT8+M1+ and OKT8+M1-subsets and used in the assay, both cell fractions suppressed B cell response in aged donors, while this effect was mediated by OKT8+M1+ cells only in the young counterpart. Soluble suppressive factors were responsible for the observed activity, since indomethacin supplementation to cultures or overnight incubation of cells before PWM stimulation abrogated the OKT8+M1--mediated suppression. Taken together, these findings suggest an additional alteration of T-B cell relationship in the elderly.

Aged↗
PubMed1987

Functional properties of Salmonella minnesota Rb-bound and Rb-unbound cell fractions in elderly donors.

The capacity of Salmonella minnesota R345 (Rb) binding to human peripheral blood lymphocytes allows the recovery of Rb-bound and Rb-unbound cell populations that elicit different functions. Here, we have applied this method to lymphocytes from aged individuals to evaluate the possibility that such an approach could reverse the senescence-related impaired immune responsiveness. In this regard we show that Rb binding augments either spontaneous or T-dependent plaque-forming cell generation in Rb-unbound fraction. By contrast, Rb-bound cells are enriched for lymphocytes releasing several lymphokines. This experimental approach seems to represent a useful tool to elucidate better the age-related alterations of the immune function.

Aged↗
PubMed1987

Immunoregulation in aging.

Senescence of the immune system leads to a decline of functional capacities of lymphoid cells. In this regard, evidence has been provided for a reduction of T and B cell-mediated responses. T-B regulation is also affected by the aging process. Since the proportion of lymphocytes is similar to that observed in young donors, either intracellular or extracellular factors may play an important role in the impaired immunoresponsiveness. An intrinsic defect of T or B cells has been in fact postulated. However, soluble suppressive factors or decreased LK production seem to represent the key events involved in the decline of the immune response. Nevertheless, over the past few years emphasis has been given to the increased lymphocyte membrane microviscosity in the elderly [Rivnay et al: Mech Ageing Dev 10: 71-79, 1979]. All together, these findings suggest a multifactorial therapeutic approach for the correction of the impaired immune response in aged individuals.

Aging↗
PubMed1986

Inhibition by antibiotics of Rb Salmonella binding to human peripheral blood lymphocytes.

Several lines of evidence point out that Salmonella minnesota R345 (Rb) possesses the capacity to adhere spontaneously to human peripheral blood lymphocytes. The binding is mediated via the lipopolysaccharide moiety of the bacterial outer membrane. In this report, we have evaluated the effects of various antibiotics on bacterial binding. Our data show that trimethoprim/sulphamethoxazole, chloramphenicol and erythromycin significantly decrease Rb binding, while gentamicin and sisomicin are without effect. Antibiotics display their inhibitory effect by acting on peripheral blood lymphocytes likely by competing with lipopolysaccharide for receptor binding capacity on lymphocyte surface.

Anti-Bacterial Agents↗
PubMed1986

Relationship between immune system and gram-negative bacteria. Acid-treated Salmonella minnesota R595 (Re) enhances immune responsiveness in patients with gynecologic malignancies.

Nine patients with gynecologic malignancies (six cervix, two endometrium and one ovary) were injected with acid-treated Salmonella minnesota R595 (Re). Patients received a total of four injections (at increasing doses from 0.5 to 3 micrograms) every 2 weeks. All patients, before treatment, had a severe impairment of their immune system either of cell-mediated immunity (leukocyte inhibiting factor activity) or non-specific immunity (polymorphonuclear cell and/or monocyte-mediated phagocytosis and killing). In contrast, the same patients displayed a normal Natural Killer cell frequency in their peripheral blood as evaluated in an agarose-single cell cytotoxic assay. At the end of the immunotherapeutic regimen, all the above immune functions significantly augmented likely via an immunomodulating effect exerted by the lipid A portion of Salmonella minnesota Re which represents the lipopolysaccharide molecule in these bacteria. This suggests a potential role for lipid A in the treatment of cancer-related immunodeficiency.

Cytotoxicity, Immunologic↗
PubMed1986

Phagocytosis of Leishmania infantum promastigotes by monocytes isolated from Leishmania-infected dogs.

Fifteen dogs with generalised leishmaniasis have been evaluated for their monocyte capacity to ingest Leishmania promastigotes. These cells displayed a lower phagocytic ability when compared to monocytes recovered from normal dogs. Moreover, sera from Leishmania-infected dogs caused a remarkable decrease of monocyte phagocytic ability in healthy dogs, whereas sera from healthy dogs could restore monocyte phagocytosis in sick animals. Similar results were seen when Candida albicans was used as stimulant. Interestingly, supernatants from polyethylenglycole (PEG) treated sera from Leishmania-infected dogs did not inhibit monocyte phagocytosis either in the autologous or in the homologous (healthy dogs) system. This suggests a possible role for serum factor(s) in the impairment of phagocytosis in Leishmania infection.

Animals↗