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Biomedical subjects

F Capsoni

Publications and source records attributed to F Capsoni.

15 recordsLinked to original sources
PubMed1992

Immunopharmacological activity of cefodizime in young and elderly subjects: in vitro and ex vivo studies.

The biological response modifying activities of cefodizime (CDZ), a new third-generation cephalosporin, were investigated in vitro and ex vivo. In vitro investigations using cells isolated from the blood of young healthy donors showed no stimulating activity of CDZ on peripheral blood lymphocytes, natural killer cell activity, IL-1 production by adherent mononuclear cells, PMN chemiluminescence or PMN chemotaxis. A slight but statistically insignificant increase in PMN phagocytosis and phagocytic index was observed in the same population. IL-1 production was increased in three subjects with low resting state values. In a controlled ex vivo study, 20 healthy elderly subjects selected on the basis of depressed phagocytic function were treated with CDZ 1 g i.m. b.i.d. or placebo for eight days. PMN function was determined at baseline and on the day after the last dose. In the CDZ group a significant increase in both phagocytosis and phagocytic index was found, while there were no changes in the placebo group. In conclusion, CDZ restored depressed PMN phagocytic function in a population of elderly subjects. Patients with impaired PMN function who require antibiotic treatment may benefit from this activity of CDZ.

Adult↗
PubMed1992

Monocyte-derived macrophage function in HIV-infected subjects: in vitro modulation by rIFN-gamma and rGM-CSF.

We investigated monocyte-derived macrophage function in 25 HIV-positive patients, 19 in the CDC class III and 6 class IV; 17 were intravenous drug abusers (IVDA) and 8 were homosexual men. Macrophages from HIV-positive patients behaved normally in assays of superoxide anion (O2-) production and candidacidal activity. After 3 days' treatment with 200 U/ml recombinant interferon-gamma (rIFN-gamma) or 250 U/ml recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF), both control and HIV-positive patients' phagocytes expressed the activated state, as indicated by the increased O2- production in response to phagocytable or soluble stimuli; however, these cytokines did not enhance candidacidal activity. Compared to appropriate HIV-negative controls (18 healthy heterosexuals, 4 homosexuals and 4 IVDA), macrophages from 19 of the 25 HIV-positive patients presented a significant defect in their Fc receptor (FcR)-dependent phagocytosis, independently from the CDC stage, AZT therapy, or life style. Treatment of macrophages with rIFN-gamma impaired their capacity to ingest IgG-coated erythrocytes, both in controls and HIV-positive subjects. Treatment of phagocytes with rGM-CSF significantly increased their FcR-dependent phagocytosis in controls, whereas in HIV-positive patients and in HIV-negative homosexuals and IVDA only an upward tendency was observed. Although the mechanism of the impaired FcR-dependent phagocytosis in HIV-positive patients remain to be clarified, our results suggest that this functional defect may be secondary to phagocyte priming by circulating IFN-gamma in vivo. This macrophage alteration may be implicated in the immunodeficiency of HIV-positive patients. However, considering the potential role of FcRs in HIV infection enhancement, the defective FcR function might even be a protective mechanism against FcR-mediated HIV dissemination. In the light of these findings, the immunotherapeutic potential of IFN-gamma and GM-CSF in HIV infection merits further investigation.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Increased expression of IgG Fc receptor type I on neutrophils and monocytes from HIV-infected subjects.

Interferon-gamma (IFN-gamma) induces de novo expression of IgG Fc receptor type I (FcRI) on neutrophils and significantly raises the level of these receptors on monocytes. Since increased concentrations of IFN-gamma have been observed in sera from patients with HIV infection, FcRI expression might also be increased on these subjects' phagocytes. FcRI expression was assessed by indirect immunofluorescence staining of phagocytes in whole blood from 40 healthy controls and 55 HIV+ subjects, 24 belonging to CDC class III and 31 to CDC class IV; 42 were intravenous drug abusers (IVDA) and 13 were homosexual men. Plasma levels of IFN-gamma were measured using a modified immunoradiometric assay. The mean linear fluorescence intensity, used as a relative measure of receptor expression, was significantly higher on unseparated neutrophils from HIV+ subjects in CDC classes III (P < 0.001) and IV (P < 0.0001) than from controls. Similar changes in FcRI expression were observed on monocytes from HIV+ subjects. While no differences were observed between IVDA and homosexual HIV+ patients, there was a significant association between FcRI expression and the patients' CDC stage, those in class IV having the highest FcRI levels. Plasma IFN-gamma concentrations were significantly higher in HIV+ patients than in controls and a positive correlation with the stages of HIV infection was again observed. FcRI expression was also increased on freshly purified neutrophils from five HIV+ patients in CDC class IV but did not increase further after 18 h incubation with IFN-gamma, a treatment that up-regulated FcRI expression on control neutrophils. These data suggest that: (i) FcRI evaluation may be a sensitive marker for the biological activity of IFN-gamma in vivo; (ii) phagocytes from HIV+ subjects are activated in vivo by IFN-gamma, expressing increased levels of FcRI; (iii) these IFN-gamma-activated cells may play a role in the pathogenesis of AIDS.

Adult↗
PubMed1992

Membrane expression and function of complement receptors CR1 and CR3 on neutrophils from HIV-infected subjects: modulation by rTNF-alpha and rGM-CSF.

We evaluated membrane expression and function of complement receptors CR1 and CR3 on neutrophils from 27 HIV-positive (HIV+) subjects (14 in the CDC class III and 13 class IV) as well as their modulation in vitro by recombinant tumour necrosis factor-alpha (rTNF-alpha) and granulocyte-macrophage colony stimulating factor (rGM-CSF). While CR1 was expressed at similar levels on neutrophils from controls and HIV+ subjects, CR3 expression was significantly higher in CDC class IV subjects than in healthy controls. CR1 and CR3 expression was significantly increased after treatment of neutrophils with both cytokines, without differences between controls and HIV+ subjects. Similarly, the superoxide anion (O2-) production in response to C3-coated zymosan (C3zy) was significantly enhanced on neutrophils from CDC class IV subjects when compared with controls. rGM-CSF and rTNF-alpha treatment significantly enhanced the spontaneous as well as C3zy-stimulated O2- production by neutrophils from controls and CDC class III subjects, and induced an upward trend in the CDC class IV group. These results indicate that the neutrophils of HIV+ patients are preactivated in vivo but they also indicate that these cells may correctly respond to a subsequent particulate stimulus as well as to activating cytokines. Our findings suggest that desensitization or functional exhaustion of complement receptors are not implicated in the abnormalities observed on neutrophils from HIV+ patients.

Adult↗
PubMed1991

Increased expression of C3b and C3bi receptors on human neutrophils and monocytes induced by a glycoprotein extract from Klebsiella pneumoniae (RU41740).

RU41740 is a glycoprotein extract from Klebsiella pneumoniae with immunomodulating properties under different experimental conditions. In particular the compound is able to stimulate several functions of human phagocytes in vitro and ex vivo. Using monoclonal antibodies and flow cytometry, in this work we assessed the effect of RU41740 on surface expression of receptors for C3b (CR1) and C3bi (CR3) in human phagocytic cells in vitro. The incubation of whole blood with varying RU41740 concentrations led to a dose-dependent increase in surface expression of CR1 and CR3 on both neutrophils and monocytes when compared with control samples incubated in buffer alone. The maximal drug-induced enhancement of complement receptors was: 291% +/- 13.4% for CR1 and 265% +/- 8.5% for CR3 in neutrophils; 117% +/- 4.5% for CR1 and 98% +/- 4.1% for CR3 in monocytes. These peak effects were observed using RU41740 at a final concentration of 10 micrograms/ml and were similar to those induced by optimal concentrations of the activating compound N-formyl-methionyl-leucyl-phenylalanine (10(-7)M). Polymyxin B did not modify the RU41740-induced enhancement of CR1 and CR3 expression on phagocytes, suggesting no role for endotoxin in this activity. These results define, at least in part, the mechanism of action of RU41740 on human phagocytes in vitro and could be relevant to in vivo events during RU41740 treatment.

Adjuvants, Immunologic↗
PubMed1991

The effect of cytokines on human neutrophil Fc receptor-mediated phagocytosis.

The recombinant (r) cytokines interferon-gamma (rIFN-gamma), granulocyte/macrophage-colony stimulating factor (rGM-CSF) and tumor necrosis factor-alpha (rTNF-alpha) all activate neutrophils. The aim of this work was to determine the effect of these cytokines on neutrophil Fc-receptor (FcR)-mediated phagocytosis and membrane expression of FcR, particularly FcRII and FcRIII. A short treatment (greater than or equal to 15 min) of neutrophils with rGM-CSF and rTNF-alpha at concentrations greater than or equal to 62.5 U/ml significantly increased their ability to bind and phagocytize IgG-coated erythrocytes (EA). Both cytokines also showed more enhancing activity when suboptimally sensitized EA were used for binding and ingestion assays. A similar treatment of neutrophils with rIFN-gamma at doses up to 500 U/ml was ineffective. The effect of rGM-CSF and rTNF-alpha was blocked by a monoclonal anti-GM-CSF antibody and by a polyclonal anti-TNF-alpha antibody respectively, thus establishing that the cytokines were responsible for the activity of the recombinant preparations. The cytokine-induced enhancement of FcR-mediated phagocytosis did not correlate with an enhancement of FcRII membrane expression on treated neutrophils; rGM-CSF significantly increased FcRIII expression, but rTNF-alpha and rIFN-gamma were both ineffective in this respect. Since different roles of FcRII and FcRIII have been reported on ligand binding and ingestion, we also studied the effect of rGM-CSF and rTNF-alpha on the functional properties of these FcR, using specific monoclonal antibodies (mAbs). In the blocking experiments the pretreatment of neutrophils with rGM-CSF and rTNF-alpha did not modify the blocking properties of either anti-FcRII or anti-FcRIII mAbs, suggesting that cytokine-pretreatment does not affect the individual contribution of each type of FcR to ligand binding and internalization. Our data point to a new activity for both rGM-CSF and rTNF-alpha in augmenting FcR-mediated phagocytosis on neutrophils, but the mechanism of this enhancement remains to be elucidated.

Cell Adhesion↗
PubMed1979

The role of superoxide anion generation in antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity.

Human polymorphonuclear leukocytes (PMNs) can act as killer cells in an antibody-dependent cellular cytotoxicity (ADCC) system. Cytolysis is rapid and detectable at low effector/target cell ratios. PMNs from a patient affected by chronic granulomatous disease (CGD) exhibit an absolute defect in ADCC. In order to investigate the role of the toxic oxygen derivatives (H2O2 and superoxide anions) lacking in CGD, experiments in presence of specific inhibitors were carried out. Superoxide dismutase, an O-2 scavenger, displayed a significant inhibition activity in a dose dependent way. On the other hand neither catalase, which degrades H2O2, nor sodium azide, a myeloperoxidae inhibitor, affect the cytotoxic activity. Our results suggest that the importance of the intact oxidative metabolism in PMN-mediated ADCC against chicken red blood cells could be referred to the correlated production of O-2 anions.

Animals↗
PubMed1977

IgG and C3 receptors on polymorphonuclear leukocytes in phagocytosis. Role of C3-receptors in the attachment and ingestion phases.

The role of IgG and complement (C3) receptors in the adhesion and ingestion phases of immune complexes by normal human polymorphonuclear leukocytes (PMN) were examined. The immune complexes were sheep red cells (E) sensitized with IgG (EA) or IgM antibodies plus complement (EAC'). Both types of receptor sites are involved in the adhesion phase. Moreover IgG receptors are primarily involved in the ingestion phase. Nevertheless even C3-receptors may be sufficient for complete phagocytosis. Even if EAC' adhesion was still high, C3-receptor specific phagocytosis decreased parallel with the amount of the complement used for EA19S sensibilization. The role of receptor sites on human PMN in adhesion and ingestion phases is discussed.

Binding Sites, Antibody↗
PubMed1976

[Demonstration of a granulocyte defect in aged persons correlated with the presence of autoantibodies].

Assessment of PMN leukocyte function and search for autoantibodies were performed in 36 aged human subjects (more than 60 years of age) and in 15 younger controls (40 to 60 years of age). Autoantibodies were found in 15 of the 36 aged subjects, and in none of the controls. Leukocyte function defects were therefore correlated to old age and to markers of autoimmunity. Phagocytosis of bacteria was significantly impaired in both groups of old-aged subjects, irrespective to the presence or absence of autoimmunity. Intracellular killing of bacteria was shown to be normal in all the examined subjects. Nitroblue tetrazolium reduction by resting and latex-stimulated leukocytes was significantly impaired only in the group of old-aged subjects with autoimmunity. These leukocyte function defects are similar to those already described in human autoimmune diseases -- particularly S.I.E. -- and confirm the possible association between P.M.N. dysfunction and autoimmunity.

Adult↗
PubMedDate not supplied

Immunostimulation of neutrophil phagocytic function by RU41740 (Biostim) in elderly subjects.

On this randomized, double-blind trial we investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae, on human neutrophil function after oral administration to elderly subjects with a previously demonstrated phagocytic defect. Six subjects were given RU41740 orally at a daily dose of 2 mg for one week the first month and of 1 mg for one week the second month, while six subjects received placebo. Already after the first week of treatment with RU41740 (T1) and more evidently 3 weeks after the last administration of the first course of therapy (T2), a significant improvement of the neutrophil phagocytic capacity was observed; at the time T2, as well as at the end of the second course of therapy (T3), the phagocytic capacity was completely restored with no differences between control and aged subjects. Similar results were obtained in the chemiluminescence assays. As expected, placebo had no significant effect on neutrophil functions. No significant differences were observed between the two group of elderly subjects for total or differential leukocyte number. These results suggest that RU41740 exerts, almost in part, its clinical effect, i.e. the prevention of recurrent infections, by stimulating blood neutrophil phagocytic function.

Adjuvants, Immunologic↗