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Biomedical subjects

F Dallegri

Publications and source records attributed to F Dallegri.

At least 91 records · Page 5Linked to original sources
PubMed1984

Phagocytosis-dependent neutrophil-mediated extracellular cytotoxicity against different target cells.

Normal human neutrophils, incubated with 0.2 mg/ml opsonized zymosan particles, were found to lyse human (H), ox (O) and chicken (C) red blood cell (RBC) targets as determined by the 51Cr release assay. The susceptibility to the lysis of the different target cells was HRBC less than ORBC less than CRBC. An intact neutrophil metabolic burst was essential for the cytotoxic event, since neutrophils from a patient with chronic granulomatous disease failed to kill all three target cells. HRBC and ORBC destruction was prevented by catalase and unaffected by azide, suggesting the requirement of hydrogen peroxide alone in the lethal hit. CRBC destruction was abolished by catalase and azide, suggesting the involvement of the myeloperoxidase-hydrogen peroxide system. Thus, different neutrophil cytolytic systems may become operative and may vary in their efficiency depending on the type of target cells.

Animals↗
PubMed1984

Chemotactic peptide enhancement of PMA triggered monocyte cytotoxicity.

The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), per se incapable of triggering cytotoxicity, was found to significantly enhance phorbol myristate acetate (PMA)-dependent monocyte-mediated cytolysis of human red blood cell (HRBC) targets. Target cell lysis by PMA triggered monocytes was related to the release of superoxide anion and hydrogen peroxide, since cells from patients with chronic granulomatous disease and cells from normal donors, in the presence of superoxide dismutase or catalase, failed to exert significant cytotoxicity. An increased release of these mediators was found to be responsible for the FMLP-dependent amplification of the cytolytic reaction. The results indicate that chemotactic factors are able to enhance the release of cytotoxic mediators by monocytes and raise the possibility that cellular processes during monocyte chemotaxis could modulate the subsequent cytolytic activity.

Cytotoxicity, Immunologic↗
PubMed1984

Naturally-occurring cellular cytotoxicity mediated by neutrophil polymorphonuclears: requirements for the target cell lysis.

The purpose of the present study was to investigate the general conditions under which neutrophil polymorphonuclears (PMN) mediate antibody-independent cytolysis in the presence of normal human serum (NHS). Normal PMN were found to kill rabbit red blood cells (RRBC) only when cultured with 1% NHS. NHS was per se incapable of lysing RRBC. PMN from a patient with Chronic Granulomatous Disease did not destroy RRBC targets even in the presence of 1% NHS. In addition, cytotoxicity by normal PMN was significantly reduced by scavengers of oxygen metabolites. The results suggest that the target cell lysis by PMN in the presence of NHS requires a synergistic interaction between at least two mediators: serum factor(s) and oxygen metabolite(s).

Animals↗
PubMed1984

Neutrophil-mediated cellular cytotoxicity induced by zymosan-activated serum.

Human neutrophils, incubated in the presence of zymosan-activated serum ( ZAS ), were able to damage ox red blood cells ( ORBC ) as assessed by a 4-hr 51Cr-release assay. Cells from a patient with chronic granulomatous disease were incapable of mediating ZAS -induced cytolysis. Cytotoxicity by normal neutrophils was prevented by N-ethyl-maleimide as well as by catalase, but heat-inactivated catalase and superoxide dismutase were completely ineffective. Heme enzyme inhibitors, azide and cyanide, only partially reduced the target cell lysis. The results indicate the involvement of products of the oxidative metabolism, mainly hydrogen peroxide, as cytolytic mediators. These mediators released by neutrophils may contribute to the tissue injury occurring during inflammation.

Azides↗
PubMed1983

Ox erythrocyte cytotoxicity by phorbol myristate acetate-activated human neutrophils.

Human neutrophils activated by phorbol myristate acetate were cytotoxic to ox erythrocytes, as determined by the 51Cr release method. Maximal cytolysis was obtained with a phorbol myristate acetate concentration of 5 ng/ml and with an effector to target cell ratio of 1:4. An intact neutrophil metabolic burst and production of oxygen-derived-free radicals were essential for the cytotoxic event, since neutrophils from patients with chronic granulomatous disease failed to exhibit any ox erythrocyte lysis. The target cell destruction was completely prevented by catalase, was unaffected by superoxide dismutase, and was reduced approximately to one-third by azide and cyanide. These data suggest that, under our experimental conditions, the ox erythrocyte killing by phorbol myristate acetate-activated neutrophils mainly depends on myeloperoxidase and hydrogen peroxide.

Animals↗
PubMed1983

PHA-induced neutrophil-mediated cytotoxicity.

Neutrophils activated by phytohemagglutinin (PHA) were cytotoxic to chicken red blood cells (CRBC), as determined by the 51Cr release assay. High levels of cytotoxicity were obtained when one CRBC was available for each effector cell. Neutrophils from patients with Chronic Granulomatous Disease (CGD), incapable of generating potentially toxic oxygen radicals, had a reduced cytotoxicity activity, suggesting the requirement for an intact oxidative metabolism in the PHA-induced neutrophil-mediated cytotoxicity. However, CGD neutrophils maintained approximately 50% of this activity, compared with normal cells. These findings support the conclusion that both oxygen-dependent and oxygen-independent mechanisms are necessary to achieve an efficient cytotoxicity.

Adolescent↗
PubMed1983

Mechanisms of tumour cell destruction by PMA-activated human neutrophils.

Phorbol myristate acetate (PMA)-activated neutrophils were found to destroy B lymphoblast tumour cells (Raji) as determined by the 51Cr release assay. The target cell lysis was prevented by azide, suggesting the involvement of the myeloperoxidase enzyme. Catalase and cytochrome c caused a marked impairment of the neutrophil-mediated cytolysis, whereas superoxide dismutase significantly enhanced the target cell destruction. These data indicate that hydrogen peroxide plays a key role in the target cell injury; superoxide anion appears to be devoid of direct cytotoxic activity, despite its requirement as a precursor of hydrogen peroxide. The target cell destruction required the presence of the iodide ion as oxidizable co-factor for the myeloperoxidase-hydrogen peroxide system. The chloride ion alone was uneffective. Inhibition of target cell metabolic pathways, involved in the cellular defences against oxidative injury, by the anti-neoplastic agent 1,3-bis-(2-chloroethyl)-1-nitrosurea (BCNU) resulted in an increased neutrophil-mediated cytolysis. Under the experimental conditions employed, PMA-activated neutrophils incubated with BCNU-treated Raji cells became cytotoxic also in the presence of the chloride ion alone as myeloperoxidase co-factor. Our results suggest that Raji target cell destruction by PMA-activated neutrophils depends on the myeloperoxidase-hydrogen peroxide-halide system. The cytolytic event is influenced by target cells themselves, which should be regarded as an active component of the cytotoxic system, capable of interfering with the lytic mediators of the effector cells.

Burkitt Lymphoma↗
PubMed1983

Neutrophil-mediated antibody-dependent cellular cytotoxicity against erythrocytes. Mechanisms of target cell destruction.

Human neutrophils were cytotoxic to IgG coated ox erythrocytes as determined by a 51Cr release assay. Target cell phagocytosis was found to take place during the cytotoxic reaction, suggesting that cytolysis occurs as a post-phagocytic event. Studies, performed with neutrophils from patients with chronic granulomatous disease, demonstrated that these cells had an impaired cytotoxic activity, despite their ability to normally ingest target cells. Thus the cytotoxicity of human neutrophils against sensitized ox erythrocytes depends mainly on oxidative mechanisms. Oxygen radical scavengers failed to prevent the target cell lysis, possibly because of their inability to gain access into the killing sites. However, when cytotoxicity was carried out in presence of latex particles, pre-incubated with oxygen radical scavengers, a significant inhibition of target cell lysis by superoxide dismutase and cytochrome c was obtained. As well, in these experimental conditions, catalase had no effect. Furthermore, cytotoxicity was unaffected by hemeprotein inhibitors, cyanide and azide. Together, these results indicate that superoxide anion plays a key role in the neutrophil-mediated cytotoxicity against ox erythrocytes, whereas hydrogen peroxide alone or in combination with myeloperoxidase is unoperative under the experimental conditions employed.

Animals↗
PubMed1982

Disorders of neutrophil function in children with recurrent pyogenic infections.

Ten patients with neutrophil dysfunctions and recurrent pyogenic infections, mainly of the skin middle-ear, and respiratory tract, are described. The most frequently affected functions were chemotaxis and bacterial killing. Pharmacologic restoration of functional defects was tried in all cases. Levamisole was given in two cases and ascorbic acid in the other eight cases. During a follow up of at least 18 months, seven patients showed a complete restoration of neutrophil function and a long-lasting clinical remission. One of the two patients with Chronic Granulomatous Disease has been free from infections for 1 year, despite persistent neutrophil dysfunction, while the other did not display consistent clinical improvement. Another patient, who was given ascorbic acid for a short period only due to non compliance, showed neither laboratory nor clinical improvement.

Ascorbic Acid↗
PubMed1982

Role of the oxidative metabolic burst in the antibody-dependent cellular cytotoxicity mediated by neutrophil polymorphonuclears.

The purpose of the present study was to investigate the mechanisms by which neutrophil polymorphonuclears (PMN) mediate antibody-dependent cellular cytotoxicity (ADCC). Under experimental conditions which allow target cell phagocytosis, PMN were found to efficiently kill IgG-sensitized ox erythrocytes, as determined by the 51Cr release assay. Inhibition of the target cell ingestion by colchicine did not affect the PMN cytotoxic activity, suggesting that target cell phagocytosis does not represent an essential step in the PMN-mediated ADCC against erythrocytes. PMN from patients with Chronic Granulomatous Disease, who have defective oxidative metabolic burst, displayed an impaired ADCC activity, which was unaffected by changes in the phagocytic capacities induced by colchicine. The results indicate that, under the experimental conditions employed, both the intracellular and the extracellular target cell destruction by PMN involve oxygen-dependent mechanisms.

Animals↗
PubMed1982

Antibody-dependent cellular cytotoxicity of leukaemic blast cells and neutrophils from patients with acute myelogenous leukaemia.

The antibody-dependent cellular cytotoxicity against ox erythrocytes by blast cells and neutrophils from six patients with acute myelogenous leukaemia and one patient with blast crisis of chronic myelogenous leukaemia was studied. Leukaemic myeloblastic and monocytic cells behaved like potent killer cells toward ox erythrocytes and their activity was comparable with that of neutrophils from leukaemic and normal subjects. The target cell destruction was positively related to the effector cell: target cell ratio and was clearly antibody-dependent since the cytotoxic effect did not involve antibody-unsensitized erythrocytes. We suggest that this experimental system, which involves the use of ox erythrocytes sensitized by purified rabbit anti-ox IgG, provides a new and sensitive method for studying antibody-dependent cellular cytotoxicity by myeloid cells.

Animals↗
PubMed1982

Enhancement of the in vitro colony-forming capacity of human T lymphocytes induced by levamisole.

The colony-forming capacity of normal peripheral blood mononuclear cells and of TG-depleted cell suspensions induced by PHA was investigated in the presence of different concentrations of levamisole. The results obtained demonstrate that: (1) the drug enhances significantly the number of colonies formed by both mononuclear cells and TG-depleted cells at concentrations ranging from 5 x 10(-6) to 5 x 10(-8 M; (2) this stimulatory activity results from a direct effect on T cells; and (3) adherent accessory cells are unaffected by the in vitro treatment with levamisole.

Cell Adhesion↗
PubMed1982

Effects of ascorbic acid on neutrophil function. Studies on normal and chronic granulomatous disease neutrophils.

Ascorbic acid is able to stimulate neutrophil oxidative metabolism in normal neutrophils, as well as other several functions of these cells, either in the normal state or in the defective one. In the present study, we have investigated the effects of ascorbic acid on the hexose monophosphate shunt (HMPS) and on the bactericidal activity of neutrophils from Chronic Granulomatous Disease (CGD) patients. Furthermore, we have investigated the effects of ascorbic acid on the antibody dependent cell cytotoxicity (ADCC) of normal neutrophils. Ascorbic acid in vitro was able to significantly improve both HMPS activity and bacterial killing of CGD neutrophils. Its prolonged administration to such patients led to consistent clinical improvement, possibly related to the enhancement of chemotaxis, although the effects on HMPS and bacterial killing seen in vitro could not be confirmed. Ascorbic acid was also able to interfere with neutrophil ADCC with different results depending on its concentration and the experimental conditions.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Stimulation of neutrophil chemotaxis, adhesiveness, phagocytosis, and hexose monophosphate shunt activity by N-(2-mercaptopropionyl)glycine.

The effects of the sulfydryl donor drug N-(2-mercaptopropionyl)-glycine (MPG) on neutrophil chemotaxis, adhesiveness, phagocytosis, and hexose monophosphate shunt activity were investigated in vitro. The drug significantly enhanced all the neutrophil functions tested when used at appropriate concentrations. The results, which are in accord with the well known inhibition of neutrophil function by sulfydryl-blocking agents, suggest the possible therapeutic usefulness of the drug in clinical conditions with defective neutrophil function.

Amino Acids, Sulfur↗
PubMed1981

Effects of N-(2-mercaptopropionyl) glycine on neutrophil locomotion.

The effects of the sulphydryl group donor N-(2-mercaptopropionyl) glycine on neutrophil locomotion were evaluated in vitro. The drug, when used at a concentration of 10(-3) M was found to stimulate the random migration and chemotaxis of normal neutrophils as a result of an enhanced rate of locomotion. The true chemotactic response was unaffected. N-(2-mercaptopropionyl) glycine appeared to exert its effect on the whole moving cell population.

Amino Acids, Sulfur↗
PubMed1981

Immunopathological studies on a case of Sweet's syndrome.

Immunopathological studies in a case of Sweet's syndrome revealed IgM- and IgE-bearing polymorphonuclear leucocytes in involved skin when the direct immunofluorescence technique was used. Circulating polymorphonuclear neutrophils showed defective chemotaxis with normal random migration, phagocytosis, killing, and hexose monophosphate shunt activity.

Aged↗