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Biomedical subjects

A Kharazmi

Publications and source records attributed to A Kharazmi.

At least 145 records · Page 8Linked to original sources
PubMed1987

Modulation of human neutrophil and monocyte oxidative burst by Legionella pneumophila sonic extract.

The effect of Legionella pneumophila sonic extract on human neutrophil and monocyte oxidative burst was studied by superoxide anion release and luminol-enhanced chemiluminescence assays. Legionella pneumophila sonic extract by itself did not stimulate neutrophils and monocytes. The sonic extract at 8-2000 micrograms/ml primed neutrophils for enhanced superoxide release and, at 8-62.5 micrograms/ml, for enhanced chemiluminescence. Monocytes were only primed for enhanced chemiluminescence at very low extract concentrations (below 16 micrograms/ml). Monocyte superoxide release was suppressed by extract concentrations higher than 2000 micrograms/ml and the chemiluminescence response of neutrophils and monocytes by concentrations higher than 250 and 125 micrograms/ml, respectively. The priming activity was heat stable and present in fractions below 5 kDa. On the basis of these findings it is suggested that enhanced production of oxygen metabolites by neutrophils in contact with legionella components at low concentrations could contribute to the lung tissue damage seen in Legionnaires' disease, whereas the suppression of phagocyte oxidative burst by higher extract concentrations may be one of the mechanisms by which Legionella pneumophila survives intracellularly.

Endotoxins↗
PubMed1987

Pseudomonas aeruginosa septicaemia in a patient with severe Plasmodium falciparum.

This report describes a Danish patient with severe Plasmodium falciparum infection and Pseudomonas aeruginosa septicaemia. The patient had been sailing along the coast of West Africa for ten years without taking any antimalaria prophylaxis and without any apparent previous history of malaria. He presented with severe form of malaria, progressing rapidly into coma and died within a short time. P. aeruginosa was isolated from his blood taken on the day of admission. His neutrophils were all occupied by P. falciparum. The unusual combination of severe falciparum malaria infection and P. aeruginosa septicaemia with extensive involvement of neutrophils lends further support for the role of phagocytic defence in malaria.

Adult↗
PubMed1987

Priming of neutrophils for enhanced oxidative burst by sputum from cystic fibrosis patients with Pseudomonas aeruginosa infection.

Neutrophils accumulate in the lungs of cystic fibrosis (CF) patients and inflict tissue damage by release of oxygen radicals and proteases. Here we report on the ability of sputum to prime neutrophils for enhanced release of oxygen radicals. Sol phase was prepared by ultracentrifugation of sputum obtained from CF patients attending the CF Clinic, Rigshospitalet, Copenhagen. The oxidative burst response of neutrophils from healthy individuals was measured by oxygen consumption, superoxide production and chemiluminescence. Neutrophils were preincubated with sputum or buffer and then stimulated with f-Met-Leu-Phe or zymosan. Appropriate controls were included in the experiments. It was shown that neutrophils preincubated with CF sol phase and stimulated with f-Met-Leu-Phe generated a three- to five-fold higher chemiluminescence response than those preincubated with buffer. There was no enhancement of the response when zymosan was used for stimulation of the cells. Neutrophils incubated with sol phase alone exhibited no response. Attempts were made to identify and partially characterize the priming factor(s). It was found that the sputum samples contained bacterial endotoxins. The priming activity was resistant to heating at 100 degrees C for 15 min, and was present only in fractions with molecules larger than 100 KD. It is suggested that the priming factor(s) consist of bacterial endotoxins and/or immune complexes. Activation and enhanced release of oxygen radicals from neutrophils may play an important role in the host defence as well as pathogenesis of tissue damage in the lungs of these patients.

Cystic Fibrosis↗
PubMed1987

Generation of reactive oxygen radicals by human phagocytic cells activated by Plasmodium falciparum.

The role of monocytes, macrophages and neutrophils in killing malaria parasites is well documented, and their involvement in malaria pathology has been suggested. However, the underlying mechanisms are not clear. The present study reports on the role of P. falciparum-parasitized erythrocytes, free merozoites, and culture supernatant antigens in the generation of reactive oxygen radicals by human peripheral blood monocytes and neutrophils. Blood neutrophils and monocytes obtained from healthy individuals were isolated by density gradient separation. A human isolate of P. falciparum was grown in continuous culture. Parasitized erythrocytes and free merozoites were prepared from synchronized cultures. Soluble antigens from culture supernatants were purified by affinity chromatography using CNBr-Sepharose 4B columns bound to specific IgG. Oxidative burst response of neutrophils and monocytes were determined by oxygen consumption, superoxide production, and chemiluminescence. It was found that P. falciparum merozoites and the soluble antigens were capable of activating neutrophils and monocytes in vitro and resulting in the production of oxygen radicals by these cells. In conclusion, these findings demonstrate that malaria antigens are able to activate normal human blood phagocytes and result in generation of oxygen radicals by these cells. The released oxygen radicals can then contribute to both the destruction of the parasite and the pathology of malaria.

Antigens, Protozoan↗
PubMed1987

Selective modulation of the CD4 molecular complex by Pseudomonas aeruginosa alkaline protease and elastase.

The binding of monoclonal antibodies against CD4 was specifically inhibited by treatment of human CD4+ cells with either alkaline protease (AP) or elastase (Ela), purified from Pseudomonas aeruginosa. Binding of antibodies against CD3 (pan T), CD5 (pan T), CD8 (T suppressor/cytotoxic), HLA-ABC, HLA-DR, HLA-DQ, HLA-DP/DR, and beta 2 microglobulin was not inhibited by AP or Ela. Heat-inactivation of the proteases at 65 degrees C for 20 min or treatment with the metal chelator EDTA abolished the inhibitory activity of both proteases. These findings may serve to develop novel immunological methods for the isolation and study of the lymphocyte CD4 structure, which plays an important part in the immune response.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Inhibition of human lymphocyte proliferative response by serum from Plasmodium falciparum infected patients.

Malaria infection has been shown to induce alterations in immune reactivity. This report describes the effect of serum obtained from Plasmodium falciparum infected patients on in vitro proliferation of human blood mononuclear cells (BMNC) isolated from healthy individuals. Serum obtained before initiation of treatment suppressed the in vitro lymphocyte proliferative response to both Plasmodium-derived antigens and an unrelated antigen (PPD-tuberculin). The suppressive effect was lost if the serum was incubated at 56 degrees C for 30 min, and the effect was not HLA-restricted since the inhibition was seen on both autologous and heterologous BMNC. The degree of suppression was not correlated to the duration of the disease, the degree of parasitemia, or the use of chemoprophylaxis. Sera from 7 patients before and from 3 patients 30 days after initiation of treatment were pooled and fractionated. It was found that the strongest suppressive activity was in the serum fraction containing molecules from 30-100 kD.

Animals↗
PubMed1987

Inhibition of human natural killer cell activity by Pseudomonas aeruginosa alkaline protease and elastase.

The present study was designed to examine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (Ela) on human natural killer (NK) cell activity in vitro. AP and Ela were found to inhibit NK cell function. Addition of alpha interferon and interleukin-2 did not abolish this inhibition of NK cell activity. Adhesion of effector to target cells was studied in a single-cell agarose assay of monocyte-depleted NK-cell-enriched cell populations. AP and Ela were shown to inhibit effector/target cell conjugate formation. Furthermore, AP and Ela inhibited the binding of the monoclonal antibody Leu-11, which reacts with the Fc receptor of NK cells. The inhibition of NK cell binding to the target cell by P. aeruginosa proteases is most likely due to proteolytic cleavage of the surface receptors involved in the binding of the effector cell to the target cell.

Cells, Cultured↗
PubMed1987

Enhancement of human natural cytotoxicity by Plasmodium falciparum antigen activated lymphocytes.

Mononuclear cells (MNC) isolated from malaria immune donors and from donors never exposed to malaria were stimulated in vitro with soluble purified Plasmodium falciparum antigens (SPag) or PPD. After 7 days of culture the proliferative response and the cytotoxic activity against the natural killer cell (NK cell) sensitive cell line, K562, were measured. It was found that SPag stimulation enhanced cytotoxic activity of MNC from donors whose lymphocytes exhibited a strong proliferative response to the antigen. MNC with low proliferative responsiveness showed increased cytotoxic activity if the MNC were preincubated with interleukin 2 (IL-2) for one hour before the start of the cytotoxic assay. SPag activation did not enhance the cytotoxic activity of MNC which did not respond to the antigen in the proliferation assay, and preincubation of these cells with IL-2 did not increase the activity. PPD stimulation enhanced the cytotoxic activity and induced strong proliferative responses in all MNC preparations. The role of NK cells in the protection against malaria is unknown, but they play a role in the protection against virus infection and in the immune surveillance against cancer. Our findings indicate that malaria antigens either directly or through the activation of immunoregulatory cells enhance the NK cell activity.

Animals↗
PubMed1986

In vitro effect of fansimef on human neutrophil and monocyte function.

The effect of Fansimef, a recently registered triple combination of mefloquine, sulfadoxine and pyrimethamine (10:25:1) on human peripheral blood polymorphonuclear and mononuclear leucocyte function was studied. At clinically obtainable concentrations Fansimef had no effect on leucocyte viability, it did inhibit neutrophil chemiluminescence and it had no effect on other major functions, such as chemotaxis, NBT reduction, superoxide production, phagocytosis and the bactericidal activity of phagocytic cells.

Blood Bactericidal Activity↗
PubMed1986

Antimalarial drugs and human neutrophil oxidative metabolism.

The effect of several commonly used antimalarial drugs on human peripheral blood neutrophil oxidative metabolism was studied. The following drugs were tested: chloroquine diphosphate, quinine HCl, mefloquine, proguanil HCl, cycloguanil, pyrimethamine, sulphadoxine, and tetracycline HCl. It was found that none of the antimalarial drugs examined, at clinically obtainable concentrations, had any inhibitory effect on neutrophil oxygen consumption, glucose oxidation, superoxide production, NBT reduction, and chemiluminescence. However, at higher concentrations chloroquine, quinine, mefloquine, and proguanil inhibited neutrophil oxidative burst. There was a slight enhancing effect on neutrophil oxidative metabolism by pyrimethamine, combination of pyrimethamine-sulphadoxine, cycloguanil and tetracycline at concentrations lower than the clinical levels.

Antimalarials↗
PubMed1986

Phagocytosis and bactericidal activity of human leucocytes under influence of antimalarial drugs.

The phagocytic and bactericidal activity of human peripheral blood leucocytes under the influence of commonly used antimalarial drugs was studied. The following drugs were used: chloroquine diphosphate, quinine HCl, mefloquine HCl, proguanil HCl, cycloguanil, pyrimethamine and tetracycline HCl. It was found that leucocytes treated with mefloquine, proguanil and cycloguanil at concentrations higher than 0.5 mg/litre showed reduced phagocytic activity against Staphylococcus aureus. None of the other drugs tested had any inhibitory effect on phagocytosis. The bactericidal ability of the leucocytes was not affected by any of the drugs. It is concluded that none of the commonly used antimalarial drugs, at concentrations obtainable in malaria prophylaxis and therapy, have any undesirable effect on the bactericidal activity of human leucocytes.

Antimalarials↗
PubMed1986

Effects of Legionella pneumophila sonicate on human neutrophil granulocyte and monocyte chemotaxis.

The interaction of L. pneumophila serogroup 1 sonic extract with human polymorphonuclear neutrophils and monocytes was studied in an in vitro chemotaxis assay. The sonicate showed heat-stable chemotactic activity towards neutrophils and monocytes. It also exhibited cytotoxicity for neutrophils but not for monocytes. Incubation and pretreatment with the sonicate at apparently non-toxic concentration resulted in inhibition of the chemotactic response of neutrophils to various chemoattractants while monocyte chemotaxis was unaffected. The inhibitory activity was reduced to one half by heat treatment of the sonicate. High endotoxic activity was demonstrated in both heated and non-heated extract. Only two antigens (nos 1 and 61) were identified in the sonicate exposed to 121 degrees C for 1 h. It is therefore suggested that the lipopolysaccharide (no. 61) of L. pneumophila could contribute to the chemotactic activity. The adverse effects exerted by L. pneumophila on neutrophils may be one of the mechanisms by which Legionella bacteria resist the normal phagocytic host defenses.

Antigens, Bacterial↗
PubMed1986

Demonstration of neutrophil chemotactic activity in the sputum of cystic fibrosis patients with Pseudomonas aeruginosa infection.

The pathogenesis of tissue damage in the lungs of cystic fibrosis patients with chronic P. aeruginosa infection is quite complex and not well understood. Inflammatory cells, particularly neutrophils, are accumulated in the damaged tissues and in the sputum. This study demonstrates the presence of a heat-stable neutrophil chemotactic factor(s) in the sputum of CF patients. The chemotactic activity seems to be associated with the endotoxin present in the sputum. Chemotaxis of sol phase sputum was determined in a modified Boyden chamber assay. It was found that the sputum obtained from the patients showed strong chemotactic activity for peripheral blood neutrophils of normal individuals. The activity was greater than twice that of casein, a strong neutrophil chemo-attractant. Sputum at about dilution of 1:50 exhibited chemotactic activity equal to that of casein. Heat treatment of the sputum at 56 degrees C for 30 min, to inactivate complement, and at 100 degrees C for 15 min, to denature other proteins, somewhat reduced the chemotactic activity, but there was still strong chemotactic activity. The presence of endotoxin was demonstrated in both the non-heated and the heated samples by LAL and rocket immunoelectrophoresis. It is concluded that the sputum of CF patients contain chemotactic activity of heat-stable nature and most likely of bacterial origin endotoxin. These factors are involved in attraction of neutrophils to the lungs and sputum of these patients and contribute to the tissue damage of cystic fibrosis.

Chemotaxis, Leukocyte↗
PubMed1986

Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria.

The host response to Plasmodia includes the production of enlarged populations of peripheral blood monocytes and tissue macrophages in the spleen and the liver. Since the hyperplasia of the mononuclear phagocyte system is believed to arise as a consequence of an enhanced blood monocyte influx, we tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half of the patients when compared with healthy control subjects. The depression was found in Plasmodium falciparum malaria as well as in P. vivax or P. ovale malaria patients. The defective responsiveness was not receptor specific, since the responses towards casein and zymosan activated serum proved to be equally suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month. No significant differences between P. falciparum and P. vivax/ovale malaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients with P. falciparum infections was similarly suppressed before treatment (54% of controls), was still defective after 3 days of treatment, and nearly normalized after 7 days (87% of controls). Furthermore, monocyte phagocytic and candidacidal activities were assessed in the same patients on admission and during the follow-up. In contrast to chemotaxis, these functions were normal in all of the patients whenever measured. In conclusion, not all cell functions were altered in concert, and the previously unreported suppression of chemotactic migration might reflect a change in blood leucocyte subpopulations, deactivation in vivo or a direct suppressive effect of plasmodia induced products.

Antimalarials↗
PubMed1986

Suppression of parasite-specific response in Plasmodium falciparum malaria. A longitudinal study of blood mononuclear cell proliferation and subset composition.

The present longitudinal study was designed to characterize immunosuppression during acute Plasmodium falciparum infection, during the treatment and up to 1 month after the acute stage. The proliferative responses of blood mononuclear cells (BMNC) isolated from non-immune and semi-immune malaria patients and controls to mitogens and two Plasmodium-derived stimulators (merozoites, Meroz, and soluble purified antigen, SPag) and non-related antigens were measured by [3H]thymidine incorporation. BMNC isolated before treatment (day 0) from the non-immune patients did not respond to Meroz, whereas those from controls showed a significantly higher response. The SPag responses were also low in BMNC isolated on day 0 and increased in both the non-immune and the semi-immune patients during the observation period. These findings indicate that during malaria there is a depression of the parasite-specific proliferative response. The subset composition of BMNC isolated from non-immune patients was studied in a FACS analyser. The mean cell volumes of both Leu 2+ and Leu 3+ cells were increased during the acute phase of the infection, indicating that malaria infection results in activation of both T-helper and T-suppressor cells. There was no overall reduction of the response to mitogens on day 0. However, 3 days after initiation of the treatment the mitogen response was decreased. This finding indicates that it is important to distinguish between the effects of malaria infection and of drug treatment.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Blood monocyte and neutrophil functions in the acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) is characterized by infections with microorganisms against which phagocytes (especially monocytes/macrophages) play an important role. Therefore, various functions of blood monocytes and neutrophils were tested in 16 patients with AIDS. Neutrophil chemotactic responses towards casein and N-formyl-methionyl-L-leucyl-L-phenylalanine were depressed in patients with a short duration of disease (n = 9), whereas they were normal in those with a longer duration (n = 5), P less than 0.05. Neutrophil superoxide anion release was normal. In contrast, we found no evidence of an altered monocyte activity in the patients, since chemotactic responsiveness, phagocytosis of opsonized Candida albicans, and superoxide anion release were all normal. These findings suggest that the depressed neutrophil chemotaxis may play an important role in the high incidence of opportunistic infections in AIDS. Furthermore, it appears that in AIDS the immune deficiency does not extend to peripheral blood monocytes, but it does not exclude the possibility that the function of tissue macrophages is abnormal.

Acquired Immunodeficiency Syndrome↗