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Biomedical subjects

K Kragballe

Publications and source records attributed to K Kragballe.

At least 181 records · Page 10Linked to original sources
PubMed1982

Divergent effects of methylxanthines and adenylate cyclase agonists on monocyte cytotoxicity and cyclic AMP levels.

The effects of theophylline, isobutylmethylxanthine (IBMX), prostaglandin E1 (PGE1), and isoproterenol on monocyte antibody-dependent cytotoxicity (ADCC) were compared with their effects on monocyte cyclic adenosine 3':5'-monophosphate (cAMP) levels. Theophylline (2 mmol/l) halved ADCC and gave a 2-fold increase in cAMP levels. At concentrations not elevating cAMP theophylline inhibited ADCC significantly. In comparison, incubation of monocytes with IBMX, PGE1 and isoproterenol ADCC was only modestly inhibited while these agents gave larger increments (3- to 8-fold) in cAMP levels than theophylline did. Low concentrations of IBMX (50 mumol/l) elevated cAMP without affecting monocyte ADCC whereas PGE1 and isoproterenol inhibited ADCC dose-dependently comparable to increases in cAMP. However, in doses giving similar inhibition of ADCC addition of PGE1 resulted in larger cAMP increments than isoproterenol. The effects of IBMX, PGE1 and isoproterenol was dependent on target cell to effector cell ratio and increased during preincubation with the agents. The inhibition of ADCC by the agents was accompanied by a depressed monocyte lysozyme release and depressed activation of hexose monophosphate shunt. However, only theophylline affected monocyte attachment to sensitized target cells. These results argue against the general inverse relationship between cAMP content and inhibition of monocyte ADCC and demonstrate that theophylline independent on increases in cAMP inhibits ADCC probably by abrogation of monocyte binding activity.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Enhanced monocyte and neutrophil cytotoxicity and normal cyclic nucleotide levels in severe psoriasis.

Eighteen patients with active psoriasis were investigated for antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by monocytes and neutrophil leukocytes. Patients with extensive psoriatic lesions showed increased ADCC whereas patients with minimal psoriasis had normal monocyte and neutrophil function. After clinical remission the ADCC became normal. No stimulatory factors in psoriatic serum could be demonstrated. The increased monocyte and neutrophil cytotoxicity in severe psoriasis is not explained by altered cyclic nucleotide levels as cAMP and cGMP levels were normal in psoriatic monocytes and neutrophils showing both increased and normal ADCC. Our results indicate that increased ADCC is secondary to the psoriatic activity.

Adolescent↗
PubMed1981

Histiocytosis X--an immune deficiency disease? Studies on antibody-dependent monocyte-mediated cytotoxicity.

Six children with histiocytosis X, all in clinical remission, were investigated for antibody-dependent cytotoxicity mediated by monocytes and neutrophils. Monocytes demonstrated a reduced cytotoxicity and a normal Fc receptor activity. Judged by light microscopy the monocytes were normal. Preincubation with the patient's serum did not influence the cytotoxicity of normal monocytes. Neutrophils from patients with histiocytosis X showed a normal cytotoxic activity. We postulate a functional defect of the mononuclear phagocyte system in histiocytosis X.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Antibody-dependent monocyte-mediated cytotoxicity in atopic dermatitis. Relation to clinical state and cyclic AMP response.

Antibody-dependent monocyte-mediated cytotoxicity was investigated in adult patients with atopic dermatitis. In patients with active dermatitis monocyte cytotoxicity was reduced. Serial studies of individual patients demonstrated that a reduced cytotoxicity in clinical exacerbation did not normalize during clinical remission. The reduced monocyte cytotoxicity was not caused by an abnormal influence of lymphocytes. During the cytotoxicity reaction a rapid and transient elevation of monocyte cyclic AMP occurred. In atopic dermatitis this elevation was decreased, but no relation was found between the monocyte cytotoxicity and the cyclic AMP response in these patients.

Adult↗
PubMed1981

Monocyte cytotoxicity after splenectomy.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by monocytes was determined in 45 adults approximately 4 years after splenectomy for either abdominal trauma or accidental injury during operation for benign gastroduodenal ulcer. Compared to controls, both groups of splenectomized persons showed increased numbers of monocytes and decreased monocyte ADCC. The decrease of monocyte ADCC was only significant in those splenectomized persons in whom accessory splenic tissue was not detectable by isotope scanning. Addition of the spleen-dependent peptide tuftsin to monocytes in vitro did not augment their ADCC. An increase serum concentration of immune complexes was neither related to the presence of splenic tissue nor to the monocyte cytotoxicity. Vaccination with pneumococcal polysaccharide had no effect on monocyte ADCC. It is suggested that the defective monocyte cytotoxicity observed in splenectomized persons without detectable splenic tissue might be relevant to post splenectomy infectious susceptibility.

Adult↗
PubMed1981

Monocyte-mediated antibody-dependent cytotoxicity. Modulation by Glycolysis and insulin.

In suspensions of purified human monocytes from 14 healthy persons the antibody-dependent cell-mediated cytotoxicity (ADCC), the lactate release, and the glucose uptake were studied. In non-stimulated monocytes ADCC correlated with lactate release and glucose uptake. Following addition of insulin a dose-related rise in ADCC, lactate release, and glucose uptake was observed. For each of the three processes the maximal insulin effect was about 30%. Most of the stimulation was seen within the physiological concentration range of insulin, and the insulin concentration resulting in 50% of the maximal effect was nearly the same for ADCC, lactate release, and glucose uptake (about 100 pM). The insulin stimulation of ADCC correlated with the stimulation of lactate release and glucose uptake. An inverse correlation between the ADCC of non-stimulated monocytes and the insulin stimulation of ADCC was demonstrated. No relationship was found between monocyte maturity and any of the three variables of monocyte function, either with or without insulin. These results indicate that, for normal monocytes, the cytotoxic capacity is closely related to the glycolysis.

Adult↗
PubMed1981

Mechanisms of decreased antibody-dependent cytotoxicity mediated by monocytes and neutrophils in atopic dermatitis.

By using IgG-sensitized erythrocytes as target cells, we found the antibody-dependent cytotoxicity mediated by monocytes and neutrophils to be depressed in atopic dermatitis. This change was accompanied by a reduction of phagocytosis of target cells by the effector cells, and also by a decreased lysozyme liberation from, and hexose monophosphate shunt activation in, the effector cells during the cytotoxic reaction. However, the binding of target cells to effector cells remained normal. In individual patients, cytotoxicity and phagocytosis were equally depressed. No relation was found between cytotoxicity and lysozyme liberation in atopic dermatitis, but a relation between cytotoxicity and hexose monophosphate shunt activity was highly significant. These results suggest that the decreased cytotoxicity mediated by monocytes and neutrophils in atopic dermatitis is caused by a diminished production of oxygen radicals during the respiratory burst. This reduced respiratory burst was not due to any defect in the enzymes responsible for this process, since the superoxide production of monocytes and neutrophils stimulated with phorbol myristate acetate was found normal in atopic dermatitis. It therefore seems that although binding of target cells to effector cells was normal, the signals created by the binding process were defective in activating monocytes and neutrophils in atopic dermatitis.

Adolescent↗
PubMed1981

Relation of monocyte and neutrophil oxidative metabolism to skin and oral lesions in carriers of chronic granulomatous disease.

Out of fifteen carriers of X-linked chronic granulomatous disease five had discoid lupus erythematosus-like skin lesions together with recurrent aphthous-like stomatitis, another five had only recurrent aphthous-like stomatitis, and the remainder were symptom-free. In individual carriers monocytes and neutrophils were equally reduced in their capacity for superoxide production, [1-14C]glucose oxidation and antibody-dependent cytotoxicity; but within he group of carriers a broad spectrum of depression was found. The degree of depression was closely related to the manifestations of clinical disease. It is suggested that the defective oxygen-dependent metabolism might play an aetiological role in the development of inflammatory diseases in carriers of chronic granulomatous disease. Two out of 10 unselected females with discoid lupus erythematosus were shown to be carriers of X-linked chronic granulomatous disease. Screening for this carrier state might therefore be of importance in these patients.

Adult↗
PubMed1980

Impaired monocyte-mediated cytotoxicity in atopic dermatitis.

Twenty-three adult patients with atopic dermatitis of different severity and extent all without present cutaneous infection were investigated for antibody-dependent cytotoxicity mediated by purified monocytes. Compared to a healthy control group the monocyte cytotoxicity was significantly decreased for patients with more widespread dermatitis. Eight patients with acute contact dermatitis and 13 patients with extrinsic asthma or allergic rhinitis showed normal cytotoxicity. Decreased monocyte cytotoxicity in atopic dermatitis was not related to the serum IgE level. In vitro cultivation of defective monocytes from atopics did not increase cytotoxicity, nor did normal monocytes preincubated with patient serum show abnormal function. In atopic dermatitis the total number of Fc receptor bearing monocytes was normal. However, the affinity of this receptor was lower than in normals. Serial studies are needed to establish whether reduced monocyte function is a basic pathophysiologic defect in atopic dematitis.

Adolescent↗
PubMed1980

Impaired monocyte cyclic AMP responses and monocyte cytotoxicity in atopic dermatitis.

Purified monocytes from 21 patients with mild and severe atopic dermatitis (AD) were compared with 22 healthy controls with respect to antibody-dependent cell-mediated cytotoxicity (ADCC) and cyclic adenosine 3',5'-monophosphate (cAMP) responses to stimulatory agents. ADCC was depressed in both severe and mild atopic dermatitis. The patients showed decreased cAMP responses to isoproterenol and histamine, the decrement being more distinct in severe atopic dermatitis. Formation of cAMP was diminished with PGE1 only in patients with severe AD. ADCC is inhibited by the agents that increase cAMP. In the severe dermatitis group reduced inhibition induced by isoproterenol, histamine, but not PGE1, was obtained. It is suggested that a general suppression of membrane activation may explain the reduced cAMP responses to various stimulatory agents and the impaired monocyte cytotoxicity.

Adolescent↗
PubMed1980

Serum beta 2-microglobulin in acute and chronic leukaemia.

The serum concentration of beta 2-microglobulin (beta 2-m) was measured in 69 patients with acute or chronic lympho- and myeloproliferative disorders. Serum beta 2-m was found significantly increased in 12 out of 14 patients with chronic lymphatic leukaemia. The serum concentration was proportional to the estimated lymphatic infiltration of tissues but inversely related to the number of circulating lymphocytes. Cytostatic treatment was followed by a decrease in serum beta 2-m, but normalization of the serum concentration was not observed. 11 patients with chronic granulocytic leukaemia all had significantly elevated serum concentrations of beta 2-m and increased serum concentrations were also found in patients with acute leukaemias. Thus, 12 out of 25 patients with acute myeloid leukaemia and all of 5 patients with acute myelomonocytic leukaemia as well as 4 out of 5 patients with acute lymphatic leukaemia had increased serum beta 2-m levels. In acute leukaemia no correlation could be demonstrated between the blood lymphocyte concentration and serum beta 2-m. Also no significant changes in serum beta 2-m were found in either remission or relapse of the acute leukaemia. It is concluded that serum beta 2-m in patients with chronic leukaemia may reflect the total amount or turn-over of leukaemic cells in the body and that repeated determinations of serum beta 2-m in these patients might be useful as an estimate of the residual leukaemic cell mass after therapy. Apart from this the determination of serum beta 2-m seems to be of little, if any, clinical use in leukaemia.

Adolescent↗
PubMed1980

Role of oxygen in antibody-dependent cytotoxicity mediated by monocytes and neutrophils.

The antibody-dependent cell-mediated cytoxicity (ADCC) by human monocytes and neutrophils was investigated by measuring the release of 51chromate from prelabeled erythrocytes coated with immunoglobulin G. ADCC was found to be positively correlated to phagocytosis of 51Cr-labeled erythrocytes and to the postphagocytic events of the effector cells, activation of the hexose monophosphate shunt, and degranulation. Exclusion of oxygen from the incubation media halved the ADCC by both cell types without affectijg phagocytosis or degranulation. Likewise, ADCC by cells from patients suffering from chronic granulomatous disease (CGD) was only half the intensity of ADCC by cells from normals. Inhibitors of mitochondrial respiration were without depressing effect of ADCC. Azide, which in addition to its blocking action on oxydative phosphorylation also inhibits catalase and myeloperoxidase, resulted in a approximately equal to 40% stimulation of ADCC by cells from normals but was without effect of ADCC by cells from CGD patients. The hydroxyl radical scavenger, mannitol, significantly depressed ADCC by cells from normals (P < 0.01) but was without effect on cells from CGD patients. Azide and mannitol also were without effect on ADCC by normal cells when oxygen was excluded. In a xanthine-xanthine oxidase system, erythrocytes were effectively lysed. This lysis was inhibited by catalase, superoxide dismutase, and mannitol. When comparable concentrations of glucose oxidase were used no lysis was observed. H2O2 either alone or in combination with azide did not lyse erythrocytes. It is suggested that ADCC by both monocytes and neutrophils is partly dependent on the generation of hydroxyl radicals by the effector cells.

Anaerobiosis↗
PubMed1980

HLA antigens in methotrexate-induced liver cirrhosis.

HLA typing was carried out in 20 psoriatics with methotrexate-induced liver cirrhosis and 44 methotrexate-treated psoriatics who at the time of investigation had not developed cirrhosis. The data were compared with results from tissue typing of 1291 healthy individuals. The antigen combination A1, B8 was found to be increased among patients with cirrhosis vis-à-vis methotrexate-treated psoriatics who did not develop liver cirrhosis. This finding is similar to data on chronic active hepatitis type A and drug-associated chronic active hepatitis. Findings of the antigen combination A1, B8 should--just as with other predisposing factors--lead to caution in liver control in psoriatics on methotrexate therapy.

Epitopes↗
PubMed1980

Antibody-dependent monocyte-mediated cytotoxicity. Serial studies in acute myeloid leukaemia.

Antibody-dependent cytotoxicity mediated by purified monocytes was determined in 42 patients suffering from acute myeloid leukaemia (AML). Compared to 9 patients with acute bacterial infection and to 42 normal controls, patients with untreated AML exhibited deeply depressed monocyte cytotoxicity. Cytotoxicity was reduced in each of the cytomorphological subgroups of AML. Patients attaining remission showed the same cytotoxicity as patients not attaining remission. During remission monocyte cytotoxicity increased significantly, but normal function was not achieved. Patients receiving chemotherapy alone exhibited the same defective cytotoxicity as patients receiving chemotherapy plus immunotherapy with Corynebacterium parvum. The termination of maintenance chemotherapy after remission for 1 year did not normalize cytotoxicity. Also the cytotoxicity of normal monocytes was not affected by patient serum. It is suggested that the reduced monocyte cytotoxicity observed in AML is related to the leukaemic process. The lack of complete normalization during the remission may indicate the continuous presence of an intrinsic defect of monocytopoiesis.

Adolescent↗