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Biomedical subjects

F Patrone

Publications and source records attributed to F Patrone.

At least 55 records · Page 3Linked to original sources
PubMed1984

Defective neutrophil mobilization to skin chambers in cancer patients.

The in vivo migration of neutrophils was evaluated in patients affected by epithelial carcinoma using the quantitative skin-chamber technique. The results demonstrated a significant impairment of the patients' neutrophil migration, which was reduced to approximately 4% of that of the controls. Patients' sera were able to inhibit the chemotactic responsiveness of normal neutrophils in vitro. It is therefore suggested that the defective in vivo migration of neutrophils in cancer patients is related to the presence of humoral cell-directed inhibitory activity. This defect of neutrophil function might contribute to the host-defense impairment of carcinoma patients.

Adult↗
PubMed1984

Neutrophil-mediated cellular cytotoxicity triggered by immobilized aggregated IgG: an in vitro model of cell injury during immune complex diseases.

Normal human neutrophils were found to destroy ox red blood-cell targets when incubated on micropore filters coated with aggregated IgG, as determined by the 51Cr release method. An intact neutrophil oxidative metabolism was essential for the cytotoxic event, since cells from patients with chronic granulomatous disease failed to exert any cytolysis. The target-cell destruction was prevented by catalase, azide, and cyanide and was enhanced by superoxide dismutase, suggesting involvement of the myeloperoxidase-hydrogen peroxide system. Neutrophil-mediated cytotoxicity was markedly amplified by the chemotactic peptide N-formyl-methionyl-leucylphenylalanine, as a result of an increased activity of the myeloperoxidase-hydrogen peroxide cytolytic system itself. This system of cytotoxicity provides a direct evidence for the neutrophil capacity of destroying bystander target cells under conditions simulating the in vivo immunologically mediated tissue injury and offers an excellent model to study events occurring during immune complex diseases.

Cytotoxicity, Immunologic↗
PubMed1984

Neutropenia and impaired neutrophil function in glycogenosis type Ib.

The impairment of different neutrophil functions has recently been reported in some patients with glycogenosis Ib and neutropenia. However, no satisfactory explanation for these findings has so far been supplied. In order to investigate this problem, we have studied neutrophil functions (random locomotion and chemotaxis, O-2 release, [1-14C]glucose oxidation and cellular cytotoxicity) in two further patients with glycogenosis Ib and neutropenia. The results show that neutrophil dysfunctions related to the involvement of both hexose monophosphate shunt and anaerobic glycolysis were variable. The heterogeneity of neutrophil functional impairment in glycogenosis Ib and their possible relationship with the basic metabolic defect of the disease are discussed.

Agranulocytosis↗
PubMed1984

Antibody-dependent killing of tumor cells by polymorphonuclear leukocytes. Involvement of oxidative and nonoxidative mechanisms.

Antibody-dependent cellular cytotoxicity (ADCC) against Raji cells was used as a model system to investigate the polymorphonuclear leukocyte (PMN) mechanisms involved in tumor cell lysis. PMN killed target cells by nonoxidative means, as indicated by the following observations: PMN from patients with chronic granulomatous disease (CGD), defective in their metabolic burst, lysed Raji cells normally; impairment of the oxidative metabolism of normal PMN by phenylbutazone did not affect ADCC. Rosenthal's inhibitor of phospholipase A2 completely prevented the lysis, suggesting the involvement of this enzyme in the target cell damage. The inhibition of the Raji cell glutathione redox cycle by carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)] increased cell susceptibility to PMN-mediated ADCC. This increment of lysis was related to oxidative killing systems. In fact, CGD PMN had an ADCC against BCNU-treated Raji cells lower than that mediated by normal PMN, but comparable to that observed with untreated targets, and phenylbutazone reduced the lysis of BCNU-treated Raji cells by normal PMN to the level observed with the use of untreated targets. The remaining ADCC against BCNU-treated Raji cells mediated by CGD PMN and by normal PMN in the presence of phenylbutazone was suppressed by Rosenthal's inhibitor. Thus PMN killed sensitized BCNU-treated Raji cells by use of both oxidative and nonoxidative means. The results indicate that the interaction of sensitized Raji cells with PMN triggers simultaneously oxidative and non-oxidative potentially lytic systems and the mediator(s) of Raji cell lysis actually operating may depend on the metabolic state of the target cells themselves. Therefore, the lysis of sensitized tumor cells might not reflect the simple effect of PMN tumoricidal systems; rather it should be regarded as a result of an inability of the target cells to escape the various PMN cytolytic mechanisms.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

Extracellular cytolysis by leukaemic blast cells.

Leukaemic blast cells from 20 patients with acute leukaemia were examined for their capacity to mediate cytotoxicity against ox red blood cells in the presence of phorbol myristate acetate (PMA), a system widely employed as an in vitro model of tissue damage by metabolically activated mature phagocytes. Blasts from certain patients with myelomonocytic and monocytic leukaemia behaved like efficient killer cells. Conversely, leukaemic myeloblasts and promyelocytes as well as leukaemic lymphoblasts were ineffective. Blast cells capable of inducing the target cell lysis were also capable of mounting an oxidative respiratory burst upon challenge with PMA, as detected by the superoxide anion release. N-ethyl-maleimide, superoxide dismutase and catalase completely inhibited the cytotoxicity by monocytoid blast cells, suggesting the involvement of oxygen reactive products in the lethal hit itself. The cytolytic potential of blasts committed to monocytic differentiation might be an additional factor contributing to the tissue damage in a subpopulation of leukaemic patients.

Adult↗
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

A monoclonal antibody to platelet glycoproteins IIb and IIIa complex: its use in purifying human megakaryocytes from sternal bone marrow aspirates for immunofluorescence studies of Ia-like antigens.

A monoclonal antibody (PBM 6.4) to platelet and megakaryocyte glycoproteins IIb and IIIa has been obtained and used to purify human megakaryocytes from sternal bone marrow aspirates by a simple method, consisting of a Percoll gradient centrifugation followed by affinity adherence on PBM 6.4-coated plastic surface, "panning." Megakaryocytes, 80-90% pure and morphologically well preserved, were attached to poly-L-ornithine-coated multi-well microscope slides and immunofluorescence was done using monoclonal antibodies to human Ia-like antigens (DR, DC1). A higher proportion of DR-positive megakaryocytes was found, in comparison to the values reported by others, while DC1 antigen was detected on about 20% of megakaryocytes. The method described has the unique feature of enriching cells of the human megakaryocytic lineage from simple diagnostic sternal aspirates in an amount adequate for immunofluorescent and morphological analysis.

Animals↗
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↗