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Biomedical subjects

F Capsoni

Publications and source records attributed to F Capsoni.

At least 19 recordsLinked to original sources
PubMed1999

Effectiveness of IFN-gamma for liver abscesses in chronic granulomatous disease.

In chronic granulomatous disease, interferon-gamma (IFN-gamma) significantly reduces the incidence and severity of recurrent infections, but its effectiveness administered ex novo during acute infection has been reported in only one case. In this report, we describe two adult brothers with chronic granulomatous disease treated successfully with IFN-gamma for acute liver abscesses. Two brothers with severe recurrent infections of unknown origin were hospitalized for septic fever, malnutrition, and ultrasonographic evidence of liver abscess. Autosomal recessive chronic granulomatous disease was diagnosed based on lack of superoxide anion production by phagocytes and absence of p47-phox protein. An antibiotic regimen specifically directed against Staphylococcus aureus was ineffective, whereas treatment with 50 microg/m2 IFN-gamma s.c. thrice weekly induced complete healing with scarring within 3 months. No septic recurrence was observed during a 4-year follow-up period. In chronic granulomatous disease, IFN-gamma is effective not only in preventing but also in healing life-threatening acute infections.

Adolescent↗
PubMed1998

Development of phagocytic function of cultured human monocytes is regulated by cell surface IL-10.

Monocytes differentiating in vitro into macrophages increase their capacity to ingest particles via FcgammaR and CR3. Because human recombinant IL-10 is a potent up-regulator of phagocytosis in human monocytes, we investigated whether spontaneously produced IL-10 could be a signal for the modulation of phagocytosis by cultured monocytes. We show here that culture of monocytes in the presence of anti-IL-10 mAb completely abolished up-regulation of phagocytosis of both EIgG and EIgMC3bi, suggesting a role for spontaneously produced IL-10 in the modulation of phagocytosis by cultured human monocytes. The inhibition exerted by anti-IL-10 mAb on the development of FcgammaR-mediated ingestion was dependent on the concomitant inhibition of FcgammaRIII induction in cultured cells. On the other hand, a similar down-regulation of CR3 expression was not involved in the inhibitory effect exerted by anti-IL-10 mAb on the development of CR3-mediated ingestion. Monocytes secreted detectable levels of IL-10 when cultured in medium but the concentrations of IL-10 in the supernatants decreased with length of time in culture, the decrease being completely reversed by anti-IL-10 mAb. In addition, we showed that monocytes expressed immunoreactive IL-10 on their surface and this expression increased during differentiation into macrophages. Whether this IL-10 was bound to specific membrane receptors or it was an integral membrane protein remains to be determined; however, this latter possibility is consistent with our observations that IL-10 did not elute with acid treatment and exogenous IL-10 did not increase surface staining of monocytes. Our data indicate that human mononuclear phagocytes express IL-10 on their membrane and suggest that this cytokine may represent an autocrine signal for the increased phagocytic function observed during differentiation of monocytes into macrophages.

Antibodies, Monoclonal↗
PubMed1997

Interleukin-10 down-regulates oxidative metabolism and antibody-dependent cellular cytotoxicity of human neutrophils.

The authors investigated the ability of interleukin-10 (IL-10) to modulate some constitutive or interferon-gamma (IFN-gamma)-enhanced activities of human neutrophils. An 18h culture of neutrophils with IL-10 dose-dependently down-regulated their capacity to produce O(2)- and lucigenin-amplified chemiluminescence in response to n-formyl-methionyl-leucylphenyl-alanine (FMLP). Furthermore, treatment of neutrophils with IL-10 decreased in a dose-dependent fashion, their capacity to lyse antibody-coated sheep erythrocytes. Membrane expression of Fc gamma RI, Fc gamma RII, Fc gamma RIII, CR1, CR3 and Fc gamma R- and CR-mediated phagocytosis were not modified by the cytokine. Culture of neutrophils with IFN-gamma (100 U/ml) did not modify their Fc gamma R- and CR-mediated phagocytosis, but significantly up-regulated Fc gamma RI and CR3 membrane expression as well as their oxidative metabolism and antibody-dependent cellular cytotoxicity (ADCC). When IL-10 and IFN-gamma were added simultaneously to neutrophil culture, IL-10 dose-dependently reduced IFN-gamma-induced increase of CR3 expression, O(2)- production (in response to both FMLP and phorbol 12-myristate 13-acetate, or PMA) and ADCC, but did not change Fc gamma RI expression on phagocytes. These results demonstrate that IL-10 is a significant neutrophil deactivator and provide new information on the role of IL-10 in the regulation of neutrophil-mediated inflammatory processes.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1996

The neuropeptide alpha-MSH has specific receptors on neutrophils and reduces chemotaxis in vitro.

The proopiomelanocortin-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH) has potent anti-inflammatory effects in all animal models of inflammation against which it has been tested. Understanding of the mechanism by which this occurs is incomplete, although there is recent evidence for alpha-MSH receptors in murine and human macrophages and for modulation of production of proinflammatory cytokines and related mediators by alpha-MSH. Because of the prominence of neutrophils in early stages of inflammatory reactions where alpha-MSH is effective, we examined human neutrophils for evidence of mRNA for alpha-MSH receptors and for inhibition of neutrophil chemotaxis. There was accumulation of mRNA for melanocortin receptor 1 (MC1) in RT/PCR product from neutrophils stimulated with interferon and LPS. In subsequent studies alpha-MSH inhibited migration of neutrophils from most normal volunteers when the cells were placed in FMLP or IL-8 gradients. The inhibition by alpha-MSH could be traced to alterations in cAMP in neutrophils. The presence of alpha-MSH receptor message in neutrophils is consistent with the established anti-inflammatory effects of the peptide. Direct inhibition of neutrophil chemotaxis likely contributes to the anti-inflammatory activity of alpha-MSH.

Analysis of Variance↗
PubMed1996

Amicrobial pustular dermatosis of cutaneous folds associated with autoimmune disorders: a new entity?

BACKGROUND: An unclassified amicrobial pustular dermatosis particularly affecting the main cutaneous folds, external auditory canals and scalp and coexisting with systemic lupus erythematosus has been recently described. OBJECTIVE: We studied 3 young females bearing such cutaneous manifestations in association with subacute cutaneous lupus erythematosus, celiac disease and various serum autoantibodies, respectively, in order to further characterize this possibly new entity. METHODS: Various routine and immunological laboratory tests, histopathologic and direct immunofluorescence examinations and in vitro studies of neutrophil function were performed in each patient. RESULTS: We reported our findings and compared our cases with the few others appearing in the literature. We documented an impaired neutrophil chemotaxis in 2 subjects, but neutrophil dysfunction does not seem to be one of the verifying criteria. CONCLUSIONS: All of these cases may represent a distinctive form in the clinicopathological spectrum of neutrophilic dermatoses (ND) because of the typical distribution and the close link with different autoimmune disorders. Cimetidine in combination with ascorbic acid can be indicated as an effective and safe alternative to the classic medications of ND, although the action of both drugs remains unexplained.

Adult↗
PubMed1995

IL-10 up-regulates human monocyte phagocytosis in the presence of IL-4 and IFN-gamma.

Interleukin-10 (IL-10), a cytokine produced by type 2 helper T (Th2) cells, inhibits the microbicidal effector function of interferon-gamma (IFN-gamma)-activated macrophages. However, recent observations indicate that IL-10, like IFN-gamma, increases Fc gamma RI expression and Fc gamma R-mediated cytotoxic activity on human monocytes, suggesting that this cytokine cannot be classified purely as a monocyte deactivator. The present study found that incubation for 40 h of human monocytes or monocyte-derived macrophages in the presence of IL-10 caused a significant enhancement of their capacity to ingest particles coated with immunoglobulin G (Fc gamma R-mediated ingestion) or with C3b/C3bi fragments of the complement system (CR1/CR3-mediated ingestion). The number of phagocytosing cells (% phagocytosis) and the number of ingested particles per cell (phagocytic index) were both significantly higher after 40-h incubation of monocytes with IL-10 concentrations > or = 1 U/ml. This up-regulating activity on phagocytosis was completely reversed by anti-IL-10 monoclonal antibody (mAb). As previously reported, IL-10 stimulated Fc gamma RI expression on monocytes but did not induce the expression of Fc gamma RII, Fc gamma RIII, CR1, and CR3. IFN-gamma, like IL-10, up-regulated only Fc gamma RI expression but significantly reduced both Fc gamma R- and CR-mediated ingestion. IL-10 almost completely reversed the IFN-gamma-induced inhibition of both Fc gamma R- and CR-mediated phagocytosis, without concomitant changes in membrane expression of phagocytic receptors. Exposure of monocytes to IL-4 reduced the membrane expression of all three Fc gamma Rs and also inhibited Fc gamma R-mediated ingestion. On the other hand, IL-4 up-regulated both CR3 expression and CR-mediated ingestion on cultured monocytes. IL-10 not only neutralized the down-regulatory effect of IL-4 on Fc gamma R expression but also completely reversed the IL-4-induced suppression of Fc gamma R-mediated phagocytosis. Exposure of monocytes to a combination of IL-10 and IL-4 resulted in a synergistic effect on CR-mediated ingestion, even though no additive effects were observed on CR membrane expression. Finally, culture of monocytes in medium containing anti-IL-10 mAb significantly reduced their capacity to ingest IgG- or C3b/C3bi-coated particles, suggesting a role for endogenously produced IL-10 in the modulation of phagocytosis by human monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1994

Fc receptors expression and function in mononuclear phagocytes from AIDS patients: modulation by IFN-gamma.

Fc-receptor (FcR)-mediated phagocytosis and FcR (FcRI, FcRII and FcRIII) membrane expression was studied on freshly separated and cultured monocytes (Mo) from 20 AIDS patients and 20 healthy controls. Both Mo and Mo-derived macrophages from AIDS patients presented a significant defect in their capacity to ingest IgG-coated erythrocytes (EA) compared to control cells. This functional defect did not depend on a decline in the number of FcR+ cells or on a decrease in the expression of FcR on their surface. In fact, the percentages of phagocytes reacting with anti-FcRI MoAb (32.2) or anti-FcRII MoAb (IV.3) were similar for controls and AIDS patients, while the percentage of FcRIII-positive Mo (MoAb 3G8) was higher in the AIDS population than in controls, though this difference was not seen on cultured Mo. The level of FcRI expression, evaluated as mean fluorescence intensity (MFI), was higher on freshly separated Mo from AIDS patients than from controls but this difference disappeared also with differentiation of Mo to Mo-derived macrophages in vitro. Parallel analysis of FcRII and FcRIII on phagocytes revealed no differences in the MFI between the AIDS and control groups. Some observations suggested that this functional defect might be secondary to phagocyte priming by circulating IFN-gamma: (1) in vitro stimulation of Mo with hrIFN-gamma, which increased FcRI expression, actually reduced phagocytosis of IgG-coated particles; and (2) IFN-gamma concentrations were increased in AIDS patients' plasma. In spite of these findings, no significant correlation was found between plasma IFN-gamma concentrations and FcR-mediated ingestion in AIDS patients, making the hypothesis uncertain. Even if the basis for the impaired FcR-mediated phagocytosis in AIDS patients remains unclear, this functional defect may have a role in the immunopathogenesis of AIDS, constituting a component cause of the immunodeficiency.

Acquired Immunodeficiency Syndrome↗
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↗
PubMed1989

A new simplified single-filter assay for 'in vitro' evaluation of chemotaxis of 51Cr-labeled polymorphonuclear leukocytes.

A new simplified radioassay for measuring polymorphonuclear leukocyte (PMN) chemotaxis is proposed using 51Cr-labeled cells and a single-filter system. The technique offers all the advantages described for the double-filter radioassay and permits a reproducible measurement of random locomotion, chemokinesis and chemotaxis. Moreover the single-filter radioassay utilizes commercially available and disposable chambers gathered in a multichamber apparatus; this makes the method very easy to learn and rapid to perform.

Cell Movement↗
PubMed1989

Bone marrow and tissue expression of gpIIb/IIIa, LFA-1, Mac-1 and gp150,95 glycoproteins.

Monoclonal antibodies (MAbs) against platelet glycoprotein gpIIb/IIIa and the leucocyte adhesion molecules LFA-1, Mac-1, and gp 150,95 alpha chain (CD11a,b,c) and beta chain (CD18) have been tested in normal and leukaemic bone marrows, in different human tissues, and in a patient with leucocyte adhesion deficiency (LAD). The effect of these MAbs on platelet aggregation was also tested. GpIIb/IIIa showed widespread distribution, while reactivity of CD11/18 antibodies was limited to haematopoietic cells. Platelets and megakaryocytes were reactive with one CD11a (25.5.2), and with no CD11b/c or CD18 MAbs. GpIIb/IIIa was present on the platelets of the patient with LAD, whereas 25.5.2, (CD11a) bound to his platelets but not to his leucocytes. These data indicate that LFA-1, Mac-1, and gp150,95 are not present on human platelets, but they suggest the existence of crossreacting epitopes on gpIIb/IIIa, which is consistent with the hypothesis that these molecules belong to a supergene family of adhesion molecules.

Antibodies, Monoclonal↗