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A Aarli

Publications and source records attributed to A Aarli.

13 recordsLinked to original sources
PubMed1998

Suppression of immunoglobulin secretion by soluble annexin II.

Annexin II (AII) belongs to a family of glycoproteins that bind negatively charged phospholipids in the presence of calcium. The annexins exert various biological functions. We have previously shown that soluble AII suppresses mitogen-induced lymphoproliferation in vitro. In this study we address the question of whether soluble AII may also affect immunoglobulin secretion. Mononuclear cells from peripheral blood were stimulated with pokeweed mitogen in vitro and immunoglobulin-secreting cells were quantified using an ELISPOT assay. Retroplacental serum and soluble AII significantly inhibited secretion of IgG and IgM when added at concentrations that did not affect lymphoproliferation or cell viability. The inhibitory effect was dose- and time dependent. Significant suppression was observed when soluble AII was added at concentrations of 0.1 and 0.01 microg/ml. The strongest inhibition was observed when soluble AII or retroplacental serum was added initially. The data demonstrate that soluble AII can suppress immunoglobulin secretion in vitro. AII seems to be a potent immunosuppressive substance. The presence of high levels of soluble AII in retroplacental serum may indicate a possible immunomodulatory role in normal pregnancy.

Animals↗
PubMed1997

Suppressive effect on lymphoproliferation in vitro by soluble annexin II released from isolated placental membranes.

PROBLEM: Syncytiotrophoblast microvillous plasma membranes (StMPM) are potent suppressors of lymphoproliferation in vitro. We have previously shown that soluble annexin II (AII) is present at higher levels in retroplacental serum (RPS) than in peripheral serum, and that soluble AII has an immunosuppressive effect. The aims of this study were to determine whether AII can be released from StMPM and whether soluble AII from StMPM exerts any immunosuppressive effect. METHOD OF STUDY: Isolated StMPM were incubated in growth medium for 18 hr and supernatants were prepared by ultracentrifugation. Soluble AII was detected by immunoblotting. StMPM, StMPM supernatant, and affinity-purified AII were analysed in a lymphoproliferation assay for immunomodulating activity. RESULTS: AII heavy chain and its p11 light chain were detected both in StMPM supernatant and in RPS after removal of StMPM particles by ultracentrifugation. StMPM, StMPM supernatant, and purified AII suppressed lymphoproliferation in a dose-dependent manner. Absorption of AII from StMPM supernatant reduced the suppressive activity. The suppressive effect of StMPM supernatant and purified AII was completely reversed by heating at 100 degrees C for 30 min or by adding recombinant interleukin-2 at 100 units/ml. Although StMPM and affinity-purified AII suppressed the proliferation of lymphocytes from all donors tested, StMPM supernatant suppressed the proliferation of lymphocytes from 12 of 23 donors. Six of eight female non-suppressed donors were multiparae, whereas five of five female suppressed donors were nulliparae. CONCLUSIONS: Annexin II is released by isolated placental membranes in vitro and is present in RPS, indicating in vivo release of AII at the fetomaternal interface, probably as AII heterotetramer. AII has immunosuppressive activity and may be important in fetal allograft survival.

Annexin A2↗
PubMed1997

Inhibition of phytohaemagglutinin-induced lymphoproliferation by soluble annexin II in sera from patients with renal cell carcinoma.

Annexin II (AII) is a member of a family of glycoproteins which bind negatively charged phospholipids in a calcium-dependent manner. Annexins are membrane-associated proteins, expressed both in normal and malignant cells, but have also been detected as soluble molecules in serum and other body fluids. Because of their adhesive properties, it has been suggested that annexins play a role in the metastatic process. An ELISA was established for quantification of soluble AII. Within-run variation was 5.2-10.4% and run-to-run variation 12.4-15.6%. Soluble AII was detected in all sera studies. A strongly positive serum was arbitrarily given the value 100 AII units and used as reference serum. The mean level in sera from 20 normal blood donors was 49 (SE 5.6) AII units. Sera from peripheral blood of five patients with renal cell carcinoma and sera from blood obtained from the renal vein of the same patients contained 47 (SE 20) and 83 (SE 28) AII units, respectively. In two patients, AII levels were increased in renal vein serum as compared with peripheral blood serum. Interestingly, in both cases, and in none of the three remaining cases, phytohaemagglutinin-stimulated lymphoproliferation was suppressed by renal vein serum as compared with peripheral blood serum. Affinity absorption of AII from the renal vein sera with increased AII levels strongly reduced their immunosuppressive activity. Addition of affinity-purified AII to cell cultures suppressed lymphoproliferation. These data show that the level of AII is markedly increased in renal vein sera from some patients with renal cell carcinoma, suggesting that AII may be locally released in vivo. The study also demonstrates an immunosuppressive effect of soluble AII in vitro. We speculate that soluble AII released by the tumour has immunosuppressive properties. This study identifies soluble AII as a novel immunosuppressive factor in sera from patients with renal cell carcinoma. A further study including a larger number of patients is currently in progress, in order to investigate the pathological significance of this finding.

Annexin A2↗
PubMed1994

Fc gamma-receptor activity of placental annexin II.

We have previously produced a MoAb, B1D6, against a placental FcR. The antigen isolated using F(ab')2-fragments of B1D6 exhibits Fc-binding properties with low affinity for IgG. The antigen is a single-chained glycoprotein with a molecular weight of approximately 37 kDa and a pI of about 7.0-8.5. Amino acid sequences from enzymatic digests of the antigen indicated that it is annexin II. Immunoreactivity using anti-annexin antisera and purified placental annexin II have further established the specificity of B1D6 to annexin II. The B1D6 epitope appears to be intramembraneous and intracellular on placental syncytiotrophoblasts, monocytes and other cells investigated.

Amino Acid Sequence↗
PubMed1993

Suppression of mitogen-induced lymphoproliferation by soluble IgG Fc receptors in retroplacental serum in normal human pregnancy.

A competitive ELISA was used to quantify soluble IgG Fc receptors (FcR) in retroplacental serum (RPS) and peripheral serum (PS) from 10 women after uncomplicated full-term deliveries. The RPS contained significantly higher amounts of soluble FcR than did PS from the same individuals. RPS suppressed phytohaemagglutinin-stimulated lymphoproliferation as compared with PS, and a positive correlation (r = 0.66) was found between the degree of suppression and the difference in soluble FcR level between RPS and PS. Absorption of sera with Sepharose 4B coupled with heat-aggregated IgG strongly reduced the immunosuppressive activity, whereas absorption with Sepharose coupled with IgG F(ab')2 fragments did not. When IgG-binding material was eluted from Sepharose beads and added to cell cultures, the immunosuppressive activity was restored. The data indicate that soluble FcR at physiological levels have immunosuppressive properties. FcR-mediated immunosuppression may be of importance for maintenance of local immunosuppression during pregnancy.

Female↗
PubMed1991

The IgG FcRII and the PI-linked IgG FcRIII trigger cytoplasmic calcium fluxes independently in human granulocytes.

The aim of this study was to investigate signal transduction through the two Fc receptors for IgG on human granulocytes. Using flow cytometry and the calcium indicator Fluo-3, we measured changes in leucocyte cytoplasmic calcium concentrations following cross-linking of cellular Fc receptors with specific antibodies. Two different approaches were used in order to study the two Fc receptors independently of each other. One was to avoid the presence of IgG Fc fragments, capable of binding to both types of receptors. The other was to use leucocytes from a patient with paroxysmal nocturnal haemoglobinuria (PNH) deficient in granulocyte FcRIII. In contrast to earlier reports, both approaches showed that the two types of IgG Fc receptors on granulocytes are capable of increasing cytoplasmic free calcium concentrations independently of each other. The results suggest that free cytoplasmic calcium ions are involved in the signal transduction pathway of both types of IgG Fc receptors on human granulocytes.

Adult↗
PubMed1991

IgG Fc receptors on epithelial cells of distal tubuli and on endothelial cells in human kidney.

IgG Fc receptors (FcR) in cryostat sections of human kidney were studied using functional assays and monoclonal antibodies (MoAbs). Using functional assays, FcR were detected on cells in glomeruli and distal convoluted tubuli, on endothelial cells and on interstitial cells. These cells were also stained with B1D6, a MoAb reactive with a 40-kD molecule with low affinity FcR activity. Using MoAbs against leukocyte FcR, a different pattern of reactivity was obtained. MoAbs against FcR I (32.2), FcR II (IV.3 and C1KM5) and FcR III (3G8 and Leu11b) stained interstitial macrophages only. The data confirm the presence of FcR on renal glomeruli and interstitial cells and also indicate that epithelial cells of distal tubuli and endothelial cells express FcR. Furthermore, renal FcR appear to be structurally different from the FcR I, II and III defined on leukocytes.

Antibodies, Monoclonal↗
PubMed1990

Signal transduction in human monocytes and granulocytes through the PI-linked antigen CD14.

A possible role for the PI-linked CD14 molecule in human monocyte and granulocyte signal mediation was investigated. Using flow cytometry and the fluorescent indicators Fluo-3 and dihydrorhodamine-123 it was shown that crosslinking of the CD14 molecule induces an increase in monocyte and granulocyte cytoplasmic calcium concentration and monocyte H2O2 production. These responses were found to be independent of IgG Fc receptors and suggest an intrinsic signal mediating capacity of the CD14 molecule.

Antigens, CD↗
PubMed1990

[Research training--the work situation of research trainees at the School of Medicine, University of Bergen].

In an investigation in spring 1989 on research training at the Medical Faculty, University of Bergen, 111 questionnaires were returned of a total of 180 distributed. 35% of the trainees were satisfied with the training, 31% not, while 30% did not know as yet. Trainees who had been full-time research fellows for two years or more (n = 33), were split in two groups with different opinions. Half of them were satisfied with the training programme, and the other half were not. The most important factor linked with the trainees' opinion of the training was personal supervision. The satisfied ones were content with supervision they had received, whereas the unsatisfied ones were not. By and large, office and laboratory conditions were adequate for the trainees, but data equipment had been supplied by many of the trainees themselves. The overall impression of this investigation is that the research training programme is working fairly well, but there is remove for improvement in the supervision of the individual trainee.

Curriculum↗
PubMed1990

[Research training--what trainees think about future research education].

A research training programme should have a clearly defined aim and a framework for accomplishment and contents. In Norway no such programme exists for the medical PhD. Present research training depends to a large extent on the individual student. The aim of this paper is to contribute to a discussion on the goals for a research programme and to report what research trainees and research fellows at the Medical Faculty, University of Bergen think is necessary as regards framework and content. 111 of 180 questionnaires were returned. On the average, the students preferred a research programme to last 4.0 years. 91 persons wanted the programme to contain a compulsory part lasting, on average, 5.5 months. The majority preferred no examination during this part of the programme. Most students wanted to maintain the present Norwegian standard for the medical PhD.

Curriculum↗