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Biomedical subjects

A Ferrante

Publications and source records attributed to A Ferrante.

At least 181 records · Page 10Linked to original sources

Stimulation of neutrophil respiratory burst and lysosomal enzyme release by human interferon-gamma.

Highly purified human interferon-gamma (IFN-gamma) induced a respiratory burst and lysosomal enzyme release in human neutrophils. The lymphokine augmented the respiratory burst induced by phorbol myristate acetate (PMA), or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), and increased the release of specific granule enzymes induced by opsonized zymosan. Viability and locomotion of neutrophils were unaffected by IFN-gamma.

Humans↗

Macrophage-neutrophil interactions: contrasting effects of the monokines interleukin-1 and tumour necrosis factor (cachectin) on human neutrophil adherence.

Incubation of human neutrophils with recombinant human interleukin-1 alpha (IL-1 alpha) resulted in the suppression of neutrophil adherence. In contrast, similar treatment with recombinant human tumour necrosis factor-alpha (TNF alpha, cachectin) resulted in the enhancement of neutrophil adherence. These contrasting effects were noted as early as 5 min after incubation, and persisted for at least 60 min. Simultaneous addition of these two monokines resulted in intermediate values between suppression by IL-1 and enhancement by TNF alpha. The stimulatory effects of the chemotactic peptide FMLP and the phorbol ester PMA were ameliorated by IL-1 but augmented by TNF alpha. The effects of these monokines on neutrophil adherence were abolished by heating but not by polymyxin B treatment, showing that their modulatory properties were not mediated by endotoxin.

Dose-Response Relationship, Immunologic↗

Staphylococcus aureus-stimulated human mononuclear leucocyte-conditioned medium augments the basal and stimuli-induced neutrophil respiratory burst and degranulation.

Culture medium conditioned by mononuclear leucocytes (MNL) stimulated by formalin-fixed heat-killed Staphylococcus aureus (sCM) modulated a number of neutrophil functions. The sCM inhibited the locomotion of human neutrophils in both the presence and absence of a chemotactic gradient generated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). It also stimulated the oxygen-dependent respiratory burst as assessed by its ability to stimulate basal H2O2, superoxide and chemiluminescence production by neutrophils. Neutrophils treated with sCM also showed increased release of lysozyme but not beta-glucuronidase. In addition, the sCM-treated neutrophils showed a potentiated response to stimuli that bind surface receptors, i.e. FMLP and opsonized zymosan. The effects of sCM and either of the stimuli were synergistic. Examination of lysosomal enzyme release showed that sCM enhanced the release of lysozyme and beta-glucuronidase induced by either FMLP/cytochalasin B or zymosan. The response to phorbol myristate acetate (PMA), which bypasses the surface receptor, was also stimulated but compared poorly with the FMLP response. The sCM effects on the FMLP-induced chemiluminescence response occurred even when FMLP addition was delayed for 4 hr. Cells treated with sCM and washed retained the ability to show an enhanced FMLP response. The neutrophil-modulating activity was not produced by MNL cultured in the absence of bacteria.

Antigens, Bacterial↗

Peripheral blood leucocyte subpopulations in patients splenectomized for trauma.

Monoclonal antibodies were used to type leucocyte subpopulations in peripheral blood mononuclear leucocytes (MNL) from patients who had had spleens removed following trauma. The proportion of OKT3+ (T) cell and OKT4+ ('T helper/inducer') cell was significantly decreased in splenectomized subjects. While a decrease was also observed for the OKT8+ ('T suppressor/cytotoxic') cells, this was not significant. The ratio of OKT4+/OKT8+ cells was significantly decreased in the splenectomized group. Interestingly, the absolute numbers of OKT3+, OKT4+ and OKT8+ cells were increased. The % of B lymphocytes (identified as Ig+ and FMC1+ cells) was significantly increased in patients. The proportion of MHC Class II+ cells (FMC4+) was also increased although not significantly. A marked increase in % of monocytes (FMC33+) was observed in patients. The changes in proportion of regulatory T cells and monocytes may in part explain the depressed mitogen responses of MNL from splenectomized subjects.

Adult↗

An enzyme-linked immunosorbent assay for the quantitation of human IgG subclasses using monoclonal antibodies.

An enzyme-linked immunosorbent assay was established for the quantitation of human IgG1, IgG2, IgG3 and IgG4 using IgG subclass-specific monoclonal antibodies. The method could detect 1-10 ng/ml of the Ig subclasses. The technique is suitable for measuring IgG subclass concentration in sera of healthy adults and in supernatants from human lymphocytes cultured in the presence of pokeweed mitogen.

Adult↗

Curative properties of muramyl dipeptide in experimental Naegleria meningoencephalitis.

Naegleria fowleri is a free-living amoeba which causes a fatal meningoencephalitis in man. Mice injected with the immunostimulant MDP or an attenuated 11RX strain of Salmonella enteritidis showed some resistance to an intranasal challenge with N. fowleri. In addition it was observed that some of the mice infected with N. fowleri and showing symptoms of naegleria meningoencephalitis, given a single injection of MDP were cured of this disease. Our findings suggest that the use of immunostimulants could be a new approach in the quest for therapeutic agents for this disease.

Acetylmuramyl-Alanyl-Isoglutamine↗

Inhibition of the respiratory burst of human neutrophils by the polyamine oxidase-polyamine system.

The addition of the polyamines, spermine and spermidine, to human neutrophils caused a depression of the hexose-monophosphate (HMP) shunt activity of neutrophils stimulated with latex particles but not of unstimulated cells. The effect was dependent on the presence of bovine serum and was not observed when normal human serum was substituted for bovine serum. The polyamine oxidase (PAO) in bovine serum was probably responsible for generating the activity since normal human serum lacks PAO. A role for PAO was further supported by the finding that partially purified bovine PAO in the presence of polyamines similarly mediated inhibition of HMP shunt activity in stimulated neutrophils. Catalase failed to prevent the inhibitory effects of the PAO-polyamine system suggesting that H2O2 is not the responsible product. In addition, our results show that human pregnancy serum known to contain PAO activity in the presence of polyamines mediated a similar inhibition of the respiratory burst.

Animals↗

Stimulation of neutrophil respiratory burst and iodination reaction by opsonized microfilariae of Dirofilaria immitis.

It has been shown that the interaction of Dirofilaria immitis microfilariae (Mf) opsonized with sera from infected but amicrofilaraemic dogs (occult dogs) stimulated the respiratory burst and degranulation of neutrophils as measured by chemiluminescence and iodination. Sera from normal and microfilaraemic dogs gave either low level or non-significant reactions. Since the sera required were also those required for neutrophil-mediated cytotoxicity to D. immitis Mf in vitro, the results suggested that the products of oxygen reduction as well as the myeloperoxidase system could be involved in the killing of Mf by neutrophils. However, whether these pathways have a major role to play in neutrophil-mediated cytotoxicity to Mf is uncertain, as various chemical and enzymatic inhibitors of the products of the respiratory burst were unable to prevent or reduce cytotoxicity. Azide, which is a known inhibitor of the iodination reaction, also failed to reduce cytotoxicity.

Animals↗

The role of the macrophage in immunity to Trypanosoma musculi.

Trypanosoma musculi was killed by adherent peritoneal exudate cells which had the typical appearance of macrophages. Observations by light and electron microscopy showed that the trypanosomes were phagocytozed and killed intracellularly within phagocytic vacuoles of mouse macrophages. Adherence, phagocytosis and killing of T. musculi required the presence of serum from mice immune to this parasite. Phagocytosis and killing of T. musculi was highly dependent on heat-labile factors in immune mouse serum.

Animals↗

Immunological reconstitution in a patient with severe combined immune deficiency using non-sibling bone marrow depleted of T cells with HuLy-m1.

An infant with severe immune deficiency received bone marrow from an HLA-A, -B, -DR matched, mixed leucocyte reaction non-reactive first cousin. The donor marrow was fractionated on a discontinuous Percoll gradient and before infusion was treated with the anti-human T lymphocyte antibody, HuLy-m1, and rabbit serum as a source of complement. Methotrexate was given during the following two weeks. A rise in the peripheral blood lymphocyte count, indicating engraftment, occurred six weeks after transplantation. There was no clinical evidence of graft versus host disease (GVHD). Engraftment has been sustained for one year and the patient is in normal health and has normal in vitro immunological function. In vitro treatment of human marrow with HuLy-m1 allows stable engraftment and may be useful in attempting to diminish or prevent GVHD.

Animals↗

Migration patterns of pathogenic and nonpathogenic Naegleria spp.

Four species of Naegleria were tested for their ability to migrate under agarose. Pathogenic N. fowleri strains exhibited rapid locomotion at 37 degrees C. Environmental isolates of N. fowleri moved faster than clinical isolates which had been kept in axenic culture for longer periods, and this result was confirmed by using the 84-2205-7 strain kept in axenic culture for 1 or 5 months. Nonpathogenic N. gruberi strains migrated actively at 28 degrees C but not at 37 degrees C; moreover, even at 28 degrees C, active amoebae constituted only a small proportion of the whole. The temperature-tolerant, nonpathogenic species N. lovaniensis moved more slowly than N. fowleri at 37 degrees C. In contrast, N. australiensis, which is temperature tolerant as well as pathogenic for mice, migrated at a rate comparable to that of N. fowleri. There appears to be a direct correlation between the locomotive ability of free-living amoebae and their pathogenic potential.

Amoeba↗

Conditioned medium from stimulated mononuclear leukocytes augments human neutrophil-mediated killing of a virulent Acanthamoeba sp.

Human neutrophils in the presence of serum containing anti-amoeba antibody either lacked amoebicidal activity or were poorly amoebicidal for Acanthamoeba culbertsoni. In contrast, neutrophils preexposed for 1 h to supernatants from human peripheral blood mononuclear leukocytes (MNLs) stimulated with phytohemagglutinin demonstrated significant amoeba killing in the presence of serum containing anti-acanthamoeba antibodies. Supernatant from MNL cultured in the absence of phytohemagglutinin were not effective in stimulating significant activity in the neutrophils. Serum containing antibody promoted the adherence of many neutrophils to one amoeba. There was no significant difference between the ability of neutrophils treated with supernatants from stimulated MNLs (stimulated conditioned medium [sCM]) and supernatants from nonstimulated MNLs (nonstimulated conditioned medium [nsCM]) in their binding to acanthamoeba. The effects of sCM on neutrophils was a general phenomenon. For example, the sCM but not the nsCM enhanced the antibody-dependent neutrophil-mediated cytotoxicity against three tumor targets (K562 erythroid myeloid leukemia cell line, B16 melanoma, and P815 (DBA/2 mastocytoma). Furthermore, the sCM but not the nsCM increased the bactericidal (against Staphylococcus aureus and Streptococcus pneumoniae) and fungicidal (against Torulopsis glabrata) activity of the neutrophil. The sCM but not the nsCM contained activities which inhibited neutrophil migration and stimulated a respiratory burst in these leukocytes. These results suggest that the neutrophil antimicrobial power can be increased by exposing the leukocytes to MNL mediators.

Amoeba↗

Differences in sensitivity of Schistosoma mansoni schistosomula, Dirofilaria immitis microfilariae, and Nematospiroides dubius third-stage larvae to damage by the polyamine oxidase-polyamine system.

The effect of the polyamine oxidase (PAO)-polyamine system on some helminths was examined in vitro. Both Schistosoma mansoni schistosomula and Dirofilaria immitis microfilariae were highly sensitive to this system, the latter more so than the former. In contrast, exsheathed third-stage larvae of Nematospiroides dubius were resistant to the effects of the PAO-polyamine system. After incubation of microfilariae with either spermine or spermidine in the presence of serum containing PAO (bovine serum or human retroplacental serum) or partially purified PAO, damage of worms occurred, compatible with our criteria for worm death. Similar results were obtained with schistosomula by using spermine. The damage seemed to be mediated by PAO products other than hydrogen peroxide because catalase did not protect either parasite. Our data demonstrate that helminths may be damaged by products of the PAO-polyamine system.

Acrolein↗

Changes in IgG and IgE antibody levels to bee venom during immunotherapy.

IgE and IgG antibodies to bee venom were measured in sera of patients receiving bee venom immunotherapy. All patients selected for therapy had suffered severe reactions to bee stings. The results showed that within 2-3 months from the commencement of immunotherapy there was a marked rise in IgG antibodies and a slight but not significant rise in IgE antibodies. After this period, the IgE antibody level began to fall and was about one third of the pre-treatment level by the second to third year. The IgG antibody level began to decline from its increased level after 9-10 months but remained above the pre-treatment level even after 2 years. All of the patients who had subsequently been accidentally stung after reaching the maintenance dosage of bee venom allergen showed no severe reactions. A small group of non-treated patients of the same category as those receiving therapy did not show a rise but a decline in the level of IgG antibodies. However, like the treated group, they showed a significant decrease in IgE antibodies. Thus one of the main benefits of bee venom immunotherapy is the build-up of a high concentrations of IgG antibodies, and this may be the critical factor in the protection against bee venom allergy.

Adolescent↗

IgG subclass deficiency in children with IgA deficiency presenting with recurrent or severe respiratory infections.

A group of 22 children presenting with recurrent or severe respiratory tract infections who had low IgA levels (more than 2 SD below the mean for age) were examined for IgG subclass deficiency. Patients were screened for possible defects in neutrophil chemotaxis, bactericidal, fungicidal, and quantitative iodination activity, as well as for complement function. The majority of the patients showed IgG subclass levels below the mean for age. Nine of the children showed definite IgG subclass deficiency and at least two showed definite deficiency of more than one IgG subclass. The predominant subclass deficiency was found to be IgG1. While nine children showed IgG4 levels below the level detectable by the technique used, it is not possible to assess whether these patients are deficient in this isotype since some healthy subjects also give values below the level of detection. Most of the patients who had very low (1-6 mg/dl) or undetectable (less than 1 mg/dl) levels of serum IgA did not show IgG subclass deficiencies, while IgG subclass deficiencies were common among those with borderline low IgA levels (slightly more than 2 SD below the mean for age). Nine children showed total IgG levels close to 2 SD below mean for age, and at least six of these showed IgG subclass deficiency. The result suggests that patients with recurrent and/or severe respiratory infections who have borderline IgA and IgG levels may have IgG subclass deficiencies and if they do could benefit from immunoglobulin therapy.

Blood Bactericidal Activity↗

Depression of human polymorphonuclear leucocyte function by anti-malarial drugs.

The effect of the anti-malarial drugs quinine, chloroquine, pyrimethamine, mefloquine and quinacrine on human polymorphonuclear leucocyte (PMN) function was examined in vitro. In general, all drugs had their greatest effect on PMN iodination reaction and locomotion, intermediate effects on PMN hexose-monophosphate shunt activity, and least effect on PMN adherence. The most potent of these were pyrimethamine and mefloquine. The PMN iodination reaction and locomotion were inhibited between 0.5-1 microgram/ml (congruent to 2-4 X 10(-6) M) pyrimethamine and 1-4 micrograms/ml (congruent to 0.25-1 X 10(-5) M) mefloquine. The study demonstrates that anti-malarial drugs depress PMN functions associated with antimicrobial activity of the cell.

Antimalarials↗