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Biomedical subjects

B K Pedersen

Publications and source records attributed to B K Pedersen.

At least 217 records · Page 12Linked to original sources
PubMed1988

Down-regulation of natural killer cell activity by autologous polymorphonuclear leucocytes. Role of indomethacin.

It has been recently reported that neutrophils are involved in the regulation of NK cell activity. However, the mechanism of such regulation is unclear. The present study was designed to investigate the mechanisms involved in the regulation of NK cytotoxicity by human neutrophils. The role of indomethacin, an anti-inflammatory drug, in this interaction was studied. NK cells were purified from peripheral blood obtained from normal individuals. NK cell cytotoxicity was tested on K 562 cell line by Cr release assay. Autologous neutrophils obtained from peripheral blood were stimulated by opsonized zymosan either in the presence or absence of indomethacin. The role of neutrophil supernatant containing oxygen radicals and prostaglandins on NK cytotoxicity was examined. It was shown that supernatants from stimulated neutrophils significantly inhibited (P less than 0.05) the autologous NK cell cytotoxicity. The presence of indomethacin in the in vitro reaction mixture, or given orally to donors, partially or completely abolished the inhibitory effect of neutrophil supernatant. Indomethacin inhibited prostaglandin E2 release, and luminol-enhanced, myeloperoxidase-mediated chemiluminescence of activated PMN. Diafiltration of neutrophil supernatant showed that the inhibitory activity was present in the fraction containing molecules lower than 5,000 daltons. In conclusion, our findings indicate that down-regulation of NK cytotoxicity is mediated by prostaglandins produced by stimulated neutrophils and possibly by oxygen radicals.

Humans↗
PubMed1988

Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases.

This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference in the effect of proteases on CD4- and CD8-positive cells. To determine the effect of proteases on interleukin-2 (IL-2)-induced cell proliferation, the proteases and IL-2 were added to the IL-2-dependent CTLL-2 cell line. AP and ELA inhibited the proliferation of these cells. When IL-2 was added in excess, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment of phytohemagglutinin-stimulated lymphocytes with AP and ELA resulted in inhibition of binding of intact IL-2 to IL-2 receptors on the stimulated lymphocytes. These results indicated that P. aeruginosa-derived enzymes are able to interfere with human lymphocyte function in vitro and that this effect might be due to cleavage of IL-2.

Binding, Competitive↗
PubMed1988

Impaired release of natural killer cytotoxic factor in patients with primary Sjögren's syndrome.

The impaired natural killer (NK) cell activity against K562 target cells of patients with primary Sjögren's syndrome (primary SS) was re-examined in a 2-year follow-up study of 10 patients and 10 normal controls. The ability of blood mononuclear cells (BMNC) to form effector/target cell conjugates and to release NK cytotoxic factor (NKCF) were studied. NK cell activity of the patients was unchanged low (P less than 0.01) compared with the controls. The number of effector/target cell conjugates did not differ between patients and controls, whereas NKCF-release from interferon-stimulated BMNC was significantly (P less than 0.01) reduced in the patients with primary SS and positively correlated to the reduced NK cell activity (r = 0.85, P = 0.0002). The permanently low NK cell activity of patients with primary SS appears therefore, at least in part, to be due to an impaired release of NKCF and not to a defective ability of effector cells to recognize and/or adhere to target cells.

Adult↗
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

Methylprednisolone pulse therapy in severe acute asthma.

In a group comparative double blind pilot study six asthmatic patients with an acute exacerbation of their disease were randomly treated with either methylprednisolone pulse therapy (MPPT) (1000 mg daily for 3 days) (n = 2) followed by placebo tablets, or standard doses of methylprednisolone (MP) (50 mg daily gradually decreased to zero over 3 weeks) (n = 4). The results showed that the effect of MPPT did not differ from that of standard doses of MP. MPPT has, however, the potential of being preferable to standard treatment with MP, because of easy administration and optimal patient compliance.

Adult↗
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↗
PubMed1987

Increase in natural killer cell activity during diethylcarbamazine treatment of patients with filariasis.

Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while that of the controls remained unchanged. We conclude that the augmentation of baseline NK cell activity, as well as interferon- and interleukin-2-enhanced NK cell activity seen in the patients, is not a direct effect of DEC, but is related to the reaction to DEC in lymphatic filariasis and onchocerciasis.

Adult↗
PubMed1987

Depressed natural killer cell activity in acute myocardial infarction.

Natural killer (NK) cell activity against K562 target cells was measured in patients within 24 h of acute myocardial infarction (AMI) and regularly thereafter for 6 weeks. NK cell activity was suppressed on days 1, 3, and 7 (P less than 0.01), day 14 (P less than 0.05) and at 6 weeks (P = 0.05) when compared to controls. Interferon, interleukin 2 and indomethacin enhanced NK cell activity on all days measured, but did not completely restore the defective NK cell activity. Serum from the patients did not suppress the NK cell activity of healthy mononuclear cells. The number of NK cells, identified as large granular lymphocytes (LGL), measured on days 1, 3, and 14 and at 6 weeks was not reduced in comparison to that of controls. Thus, the defective NK cell activity can be characterized as functional.

Adult↗
PubMed1986

Characterization of the in vitro effects of glucocorticosteroids on NK cell activity.

The NK cell activity of mononuclear cells as well as monocyte-depleted, Percoll-fractionated, NK cell-enriched effector cells against K 562 target cells was inhibited by methylprednisolone (MP) and hydrocortisone (HC) in a dose-dependent manner. The effector/target cell conjugate formation was studied in a single cell agarose assay, and it was shown that MP and HC partly inhibited the NK cell activity by inhibition of the adhesion of effector cells to target.

Adult↗
PubMed1986

Characterization of the in vivo and in vitro effects of indomethacin on human natural killer cell activity.

The in vivo and in vitro effects of indomethacin on the natural killer (NK) cell activity against K 562 target cells were studied. In vivo administration of indomethacin, 3 X 50 mg for 7 days to normal donors did not influence baseline NK cell activity, which means that treatment with prostaglandin (PG) inhibitors can be allowed in studies on NK cell activity of persons with normal PG production. The NK cell activity of fresh mononuclear cells was boosted with pharmacological concentrations of indomethacin in vitro, while frozen cells were not. Our results indicate that indomethacin enhances the NK cell activity in vitro by blocking the prostaglandin production of monocytes, since monocyte depleted effector cells were not boosted by indomethacin.

Cytotoxicity, Immunologic↗
PubMed1986

Effects of chloroquine, mefloquine and quinine on natural killer cell activity in vitro. An analysis of the inhibitory mechanism.

Natural killer (NK) cell activity against K 562 target cells was inhibited by pharmacological concentrations of chloroquine, mefloquine and quinine. The most potent were mefloquine and quinine. The drug-induced inhibition of the NK cell activity was abolished by addition of alpha-interferon (IF) or interleukin 2 (Il-2); preincubation of mononuclear cells with IF or Il-2 followed by addition of anti-malarial drugs decreased the inhibitory effects of the drugs. The drug-induced inhibition of the NK cell activity was not dependent on the presence of monocytes. Using monocyte depleted Percoll fractionated NK cell enriched populations in a single cell agarose assay, it was shown that the inhibitory effects of mefloquine, but not of chloroquine and quinine were due to an inhibition of the formation of effector/target cell conjugates.

Cell Adhesion↗
PubMed1986

Inhibition of natural killer cell activity by antigen-antibody complexes.

The natural killer (NK) cell activity of human peripheral blood mononuclear cells was found to be inhibited by precipitated tetanus toxoid anti-tetanus toxoid complexes (Te/aTe) as well as soluble Te/aTe. Preincubation of the immune complexes with protein A decreased the inhibition of NK cell activity. When mononuclear cells were preincubated with interferon (IF) or interleukin 2 (Il-2) before incubation with Te/aTe, the immune complex-induced inhibition was decreased, while IF or Il-2 added after incubation with the immune complexes had no effect. Using NK cell-enriched suspensions in a single cell agarose assay, the immune complexes were shown to inhibit NK cell activity by inhibiting the formation of effector/target cell conjugates.

Antigen-Antibody Complex↗
PubMed1986

A longitudinal study of the influence of azathioprine on natural killer cell activity.

Natural killer (NK) cell activity against K562 target cells was studied in six patients with definite or classical rheumatoid arthritis before and during treatment with azathioprine. Azathioprine induced suppression of NK cell activity, but treatment with azathioprine for 5-8 months was necessary before NK cell activity was completely suppressed. In vitro incubation of mononuclear cells from a healthy donor with azathioprine or 6-mercaptopurine in concentrations not reducing cell viability did not inhibit NK cell activity, nor did sera from patients treated with azathioprine for more than 6 months.

Adult↗
PubMed1986

Impaired indomethacin-boosting of the defective natural killer cell activity in patients with primary Sjögren's syndrome.

As it has been shown that the natural killer (NK) cell activity is depressed and the prostaglandin (PG) metabolism is disturbed in patients with primary Sjögren's syndrome (primary SS), we examined the in vitro effect of indomethacin on the NK cell activity. The NK cell activity against K 562 target cells was measured in 20 female patients with primary SS and in 18 female normal controls matched for age. Blood mononuclear cells were incubated with indomethacin (1 microgram/ml). Median baseline NK cell activity in primary SS was 15.4% (range 5.8-50.4) versus 24.7% (range 6.2-47.4) in the controls (p less than 0.05). After in vitro exposure to indomethacin median NK cell activity in the patients was 21.2% versus 34.9% in the controls (p less than 0.02). Indomethacin-enhanced NK cell activity was significantly higher than baseline NK cell activity in both patients (p less than 0.05) and controls (p less than 0.01), but the NK cell activity of the patients was significantly less enhanced than that of the controls (p less than 0.02). We conclude that the impaired indomethacin-boosting of NK cell activity in patients with primary SS probably reflects a decreased capacity of blood mononuclear cells to produce PG in vitro.

Humans↗
PubMed1986

Interleukin 2 augmentation of the defective natural killer cell activity in patients with primary Sjögren's syndrome.

Natural Killer (NK) cell activity against K562 target cells was measured in 21 female patients with primary Sjögren's syndrome (primary SS) and in 20 female normal controls matched for age. The in vitro effect of alpha-interferon (IF) and interleukin 2 (IL-2) on NK cell activity was examined and the percentage of large granular lymphocytes (LGL) in blood was measured. Median baseline NK cell activity in primary SS was 15.4% versus 24.4% in the controls (P less than 0.05). Median IF-enhanced NK cell activity in the SS group was 35.5% versus 49.6% in the controls (P less than 0.02). IL-2-enhanced NK cell activity was 35.5% versus 37.6% in the controls (n.s.) The proportion of LGL did not differ in the two groups. Median LGL/lymphocytes was 4.0% in the primary SS patients versus 4.5% in the controls (n.s.). We conclude that the defective NK cell activity in patients with primary SS is functional, as the number of LGL is normal. Further the NK cell activity off SS was restored by IL-2.

Adult↗