Biomedical subjects

R Matre

Publications and source records attributed to R Matre.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1996

Co-localization of beta 2-microglobulin and IgG in human placental syncytiotrophoblasts.

The fetal syncytiotrophoblast cells in close contact with maternal blood circulation apparently lack surface expression of HLA molecules, including the HLA light chain beta 2-microglobulin. This is thought to contribute significantly to a successful pregnancy. We find that syncytiotrophoblasts do express beta 2-microglobulin. Beta 2-microglobulin is primarily localized intracellularly in apical granules, and co-localize with human IgG. The origin and function of syncytiotrophoblast beta 2-microglobulin is unknown, but its localization in the syncytiotrophoblasts may implicate beta 2-microglobulin in the transplacental transport of IgG in conjunction with a recently identified class I HLA-like receptor for IgG/Fc. Alternatively, beta 2-microglobulin may associate with a hitherto unidentified class I HLA molecule.

Female↗

PubMed1996

Co-localization of the neonatal Fc gamma receptor and IgG in human placental term syncytiotrophoblasts.

Transfer of maternal IgG through the human placenta furnishes the newborn with passive immunity to a number of infectious agents. The exact mechanism of this transfer is still unknown, but it is agreed that it involves active receptor-mediated transport. The neonatal Fc receptor is a major histocompatibility complex class I-like receptor originally identified in the intestines of newborn rodents. A similar receptor has recently been detected in human placental syncytiotrophoblasts. Using multilabeling fluorescence immunohistochemistry and confocal laser scanning microscopy, we found that the neonatal Fc receptor co-localizes with IgG and beta 2-microglobulin in granules of human placental syncytiotrophoblast. The Fc receptor is not detected on syncytiotrophoblast apical plasma membrane. Localization to the outermost cellular barrier between the fetal and maternal blood further strengthens the role of the Fc receptor in transplacental transport of IgG.

Cesarean Section↗

PubMed1996

Characterisation of the complement-regulatory proteins decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46) on a human colonic adenocarcinoma cell line.

To avoid destruction by complement, normal and malignant cells express membrane glycoproteins that restrict complement activity. These include decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and protectin (CD59), which are all expressed on colonic adenocarcinoma cells in situ. In this study we have characterised the C3/C5 convertase regulators DAF and MCP on the human colonic adenocarcinoma cell line HT29. DAF was found to be a glycosyl-phosphatidylinositol-anchored 70-kDa glycoprotein. Blocking experiments with F(ab')2 fragments of the anti-DAF monoclonal antibody BRIC 216 showed that DAF modulates the degree of C3 deposition and mediates resistance to complement-mediated killing of the cells. The expression and function of DAF were enhanced by tumour necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta). Cells incubated with interferon gamma (IFN gamma) did not alter their DAF expression. Two MCP forms were expressed, with molecular masses of approximately 58 kDa and 68 kDa, the lower form predominating. MCP expression was up-regulated by IL-1 beta, but not by TNF alpha or INF gamma. Expression of DAF and MCP promotes resistance of colonic adenocarcinoma cells to complement-mediated damage, and represents a possible mechanism of tumour escape.

Adenocarcinoma↗

PubMed1996

Soluble complement receptor type 1 in serum and cerebrospinal fluid of patients with Guillain-Barré syndrome and multiple sclerosis.

Activation of complement is critically involved in inflammatory reactions in both Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). Soluble human complement receptor 1 (sCR1) blocks complement activation by both classical and alternative pathways. We studied serum and cerebrospinal fluid (CSF) concentrations of sCR1 in 23 patients with GBS, 27 patients with MS and 30 controls. No significant differences were found between patients and controls. Transient liver affection probably caused high serum sCR1 levels in two patients with GBS. The serum and CSF sCR1 levels were not correlated to the disease activity of GBS and MS, nor to the relapsing-remitting or chronic-progressive forms of MS. In GBS the CSF sCR1 levels correlated with the CSF total protein concentrations (r = 0.9, P < 0.01), suggesting that sCR1 leaks from serum into CSF via a damaged blood-nerve barrier. The serum sCR1 levels in GBS were slightly higher than in MS (P < 0.05). Whether this reflects changes in the release or consumption of sCR1 in these patients is at present unknown.

Adult↗

PubMed1996

Identification of the complement regulatory protein CD59 in human colostrum and milk.

PROBLEM: Complement lytic activity has been demonstrated, and a potential for its activation is present in human colostrum and milk. This necessitates the presence of regulatory mechanisms protecting epithelial cells in the oropharynx and the gastrointestinal tract of the infant, the milk cellular elements, and bacteria colonizing the oropharynx and the gastrointestinal tract. Lactoferrin and C1 inhibitor have been attributed such a role. However, it is likely that additional protection against the cytolytic activity of the membrane attack complex is required. This has lead us to investigate the presence of the complement regulatory protein CD59 in human colostrum and milk, and to further characterize the source of secretion. METHOD: Samples of human colostrum and milk were obtained from volunteers at different stages of lactation, and separated into fat, skim milk, and milk cellular elements by centrifugation. Normal human mammary gland tissues were obtained from patients undergoing biopsy for benign conditions. SDS-PAGE and Western blotting, and an immuno dot-blot assay were used to identify CD59 in human milk. Immunohistochemistry was performed on all tissue samples and cytospins of the milk cellular elements, using monoclonal antibodies to CD59. RESULTS: CD59 was present in cell-free colostrum and milk as a 19-25 kDa glycoprotein. No variation in CD59 levels was detected between colostrum and milk. CD59 was present in great amounts in the cytoplasm and was highly expressed on the surface membrane on mammary gland acinar and ductal epithelial cells, while the milk cellular elements contained CD59 mainly in their cytoplasm. CONCLUSION: The complement regulatory protein CD59 present in cell-free human colostrum and milk may exert its effects both in the mammary gland and in the oropharynx and gastrointestinal tract of the infant. The lobuloalveolar epithelial cells in the mammary gland are the likely source of secretion.

Breast↗

PubMed1996

Surface annexin II on placental membranes of the fetomaternal interface.

PROBLEM: The phospholipidbinding membrane protein annexin II has been demonstrated to possess FcR activity for IgG and has been localized to the outer part of the syncytiotrophoblast cell layer. The question has arisen whether annexin II is exposed on the surface of syncytiotrophoblast cells thus enabling it to take part in the transport of IgG across the maternal barrier. METHOD: Syncytiotrophoblast microvillous plasma membranes were analyzed by flow cytometry for annexin II as well as established surface molecules. Fresh, fixed placental tissue was preincubated with antibodies to annexin II or known trophoblast surface molecules, and analyzed by confocal laser scanning microscopy. RESULTS: Annexin II and its subunit p11 were expressed on the surface of the syncytiotrophoblast microvillous plasma membranes as were other established surface proteins (CD46, CD59, placental alkaline phosphatase), using both flow cytometry and confocal microscopy. Annexin was not detected on the surface of viable cultured trophoblast cells. CONCLUSION: Annexin II is exposed on the surface of syncytiotrophoblast cells as a heterotetramer together with its light chain p11. It is exposed to maternal blood and may be instrumental in IgG transport across the placental barrier by binding.

Alkaline Phosphatase↗

PubMed1996

Serological evidence of Lyme borreliosis in Africa: results from studies in Dar es Salaam, Tanzania.

Investigations were performed on sera from blood donors, pregnant women, patients with polyarthritis and from patients with clinical suspicion of syphilis in Dar es Salaam using Borrelia burgdorferi (Bb) flagellar antigen in a second generation ELISA test from DAKO A/S, Denmark, for specific IgM or IgG antibodies. An IgM and or IgG seropositivity rate of 30/100 (30%), 19/50 (7.2%), 10/20 (50%) and 11/20 (55%) was found in sera from the respective groups. These results compare with a Bb seroprevalence rate of 4/100 (4%), 1/52 (2%) and 363/5024 (7.2%) in blood donors, in pregnant women and in patients investigated serologically for Lyme borreliosis (Lb) respectively in Bergen, Norway, where cases of Lb are detected regularly. The high prevalence of antibodies to Bb flagellar antigen in Dar es Salaam, Tanzania where clinical conditions including erythema migrans, arthritis, mycocarditis and CNS diseases as well as tickbites are found call for further clinical, entomological and laboratory investigations.

Antibodies, Bacterial↗

PubMed1995

Cyclic variation in the expression of Fc gamma receptors in human endometrium.

Cyclic variations of Fc gamma receptors (FcR) in human endometrium were studied in specimens from the fundal part, the lower part of the uterine cavity and from the endocervix obtained in the proliferative, ovulatory and early and late secretory phase. The three classes of FcR were studied using monoclonal antibodies (mAb) and indirect immunohistochemistry with avidin-biotin-peroxidase complexes. FcRI, FcRII and FcRIII were expressed on stomal cells throughout the cycle. In the late secretory phase some of the stromal cells had morphology comparable to predecidual cells. These cells express FcRIII only. FcRIII only were expressed on the glandular epithelium in all phases of the cycle. The endothelium was negative in the midcycle and positive early and late in the cycle for FcRI and FcRIII, although weak for FcRIII late in the cycle. FcRII was not expressed on the endothelium. Apparently the FcR activity in the endometrium does not vary during the menstrual cycle, except for small variation in the expression on the endothelium and the presence of FcRIII on positive predecidual cells. No differences in FcR expression were found in specimens taken from different parts of the uterine cavity.

Adult↗

PubMed1995

The influence of tumour necrosis factor-alpha, interleukin-1 beta and interferon-gamma on the expression and function of the complement regulatory protein CD59 on the human colonic adenocarcinoma cell line HT29.

CD59 is a 18-25 kDa glycoprotein which, by inhibiting the formation of the membrane attack complex, protects homologous cells from complement mediated damage. We have described recently the expression and complement regulatory function of CD59 on colonic adenocarcinoma cells both in vivo and in vitro. In this study we have examined the influence of cytokines on the expression and complement regulatory function of CD59 on the colonic adenocarcinoma cell line HT29. CD59 expression on the HT29 cells was up-regulated after stimulation by mononuclear cells activated by mixed lymphocyte reaction and by culture supernatants from activated mononuclear cells. Similarly, a dose-dependent increase in CD59 expression was observed after stimulation with both tumour necrosis factor-alpha and interleukin-1 beta. A dose-dependent increase in the level of CD59 expression was also seen using low concentrations of interferon-gamma (IFN-gamma), while CD59 expression on cells cultured with high IFN-gamma concentrations was comparable to non-stimulated cells. Cytokine treated cells were more resistant to lysis by homologous complement than non-stimulated cells, and the increase in CD59 expression was shown to be partially responsible for this. The present data strengthen the role of CD59 as a possible participant in tumour escape.

Adenocarcinoma↗

PubMed1995

Down-regulation of CD59 (protectin) expression on human colorectal adenocarcinoma cell lines by levamisole.

The vulnerability of tumour cells to complement-mediated immune attack is regulated by membrane associated molecules. Recently, we have shown that the expression of the membrane attack complex inhibitor CD59 is enhanced on colonic adenocarcinoma cells compared to normal colonic epithelial cells. CD59 was shown, in the same study, to protect the tumour cells from complement-mediated lysis. Levamisole (LMS), used in conjunction with 5-fluorouracil as adjuvant therapy, reduces the incidence of colon cancer relapse following surgical resection. This led to our investigation of the effect of LMS on CD59 expression and function on the human colorectal cell lines HT29 and Caco-2. When cultured in the presence of 10 microM LMS, the cells reduced their expression of CD59 in a time-dependent manner. LMS treated HT29 cells were more sensitive to lysis by complement than control cells, and the reduction in CD59 expression was shown to be partly responsible for this. A reduction in CD59 expression will augment complement-mediated immune surveillance and may contribute to LMSs anti-tumour activity in vivo.

Adenocarcinoma↗

PubMed1995

Fc gamma-receptor activity in the developing human placenta.

The expression of Fc gamma receptors (Fc gamma R) and annexin II in 20 placentae (range 8-27 weeks' gestation) and in 3 full-term placentae was studied using monoclonal antibodies (mAbs) and soluble immune complexes. Functionally active Fc gamma R was detected on the trophoblast, endothelial cells, and stromal cells (Hofbauer cells) from the 8th week of gestation. Fc gamma RI (mAb 32.2) and Fc gamma RIII (mAb 3G8) were detected only on Hofbauer cells, whereas Fc gamma RII (IV3 and C1KM5) were detected both on Hofbauer cells and endothelial cells. Fc gamma RIII (anti-Leu-11b) and the IgG-binding molecule annexin II (mAb B1D6) were expressed by Hofbauer cells, endothelial cells, and the trophoblast. There was some variation in staining among the different specimens, but the number of positive cells as well as the staining intensity increased from the first to the second trimester. In first trimester placenta, staining was localized both to the syncytio- and cytotrophoblast, with the strongest intensity in the cytotrophoblast and at the boundary between the two cell layers. In second and third trimester placenta, staining was localized to the syncytiotrophoblast. The localization and distribution of Fc gamma R on the trophoblast during ontogeny is of interest with regard to its presumed role in the transport of IgG from mother to fetus.

Animals↗

PubMed1995

Antistreptolysin O and antideoxyribonuclease B titres in blood donors and in patients with features of nonsuppurative sequelae of group A streptococcus infection in Tanzania.

Antistreptolysin O (ASO) and antideoxyribonuclease B (ADN B) titres were determined on sera from blood donors in Dar es Salaam, Tanzania and from Bergen, Norway and were compared with titres in patients with features of postgroup A streptococcal diseases in Dar es Salaam. The upper limit of normal ASO titres in Dar es Salaam was 200 mu/ml and for ADN B it was 300 u/ml while in Bergen the upper limit of normal ASO titre was 250 u/ml and that of ADN B was 100 u/ml. Titres of ASO in Dar es Salaam and Bergen were consistent with those from sub-Saharan Africa and from other continents. Upper limit of normal ADN B titres in adults in Dar es Salaam were higher than those in Bergen probably due to higher frequencies of group A streptococcal skin infections in Dar es Salaam than in Bergen. Patients with features of postgroup A streptococcal diseases in Dar es Salaam had antibody titres above the upper limits of normal in 32.8% of the patients for ASO and in 45.9% for ADN B. ASO and ADN B titres or ASO and any other reliable test for antibody to group A streptococcus should be utilised together in providing strong evidence of recent infection with the group A streptococcus or of postgroup A streptococcal disease.

Adult↗

PubMed1994

A dot-immunobinding assay for the demonstration of soluble Fc gamma receptors.

We have developed a sensitive dot-immunobinding assay to demonstrate and characterize the functional activity of soluble Fc gamma receptors (FcR). Samples containing soluble FcR were immobilized on a nitrocellulose membrane. Immune complexes of horseradish peroxidase and rabbit IgG antibodies to horseradish peroxidase (HRP) were allowed to react with nitrocellulose-bound FcR, and the immune complexes were visualized by HRP developer. The intensity of the grey dots reflected the amount of immune complex bound. Binding of immune complexes to placental extract containing soluble FcR was inhibited completely by IgG and Fc fragments, but not by F(ab')2 fragments, IgA and IgM. The method was used to characterize the subclass specificity of solubilized placental FcR. Human Fc fragments, and intact IgG1 and IgG3 proteins inhibited the binding whereas preparations of F(ab')2, IgG2 and IgG4 did not. In conclusion, the dot-immunobinding assay described is a rapid and simple method for the demonstration and characterization of functionally active soluble FcR.

Antigen-Antibody Complex↗

PubMed1994

Expression and function of CD59 on colonic adenocarcinoma cells.

The expression and function of CD59, a 19-25 kDa membrane glycoprotein that inhibits formation of the membrane attack complex of complement, was analyzed on normal and malignant human colonic epithelial cells. Analysis by immunofluorescence demonstrated a weak apical expression of CD59 on normal intestinal epithelium, with an increased expression on adenocarcinoma cells. The expression of CD59 was greatest on tumor cells with poor differentiation. The functional activity of CD59 on human adenocarcinoma cells was investigated using the colonic adenocarcinoma cell line HT29. CD59 on HT29 cells was glycosyl-phosphatidylinositol-linked, and had a molecular mass of 19-25 kDa. HT29 cells expressed approximately four times more CD59 than leukocytes, and showed a high resistance to antibody-dependent complement-mediated lysis. Blocking of CD59 with divalent antigen-binding F(ab')2 fragments of the anti-CD59 monoclonal antibody 1F5 resulted in a dose-dependent increase in complement-mediated lysis, suggesting that CD59 may be of importance in protecting colonic adenocarcinoma cells against complement-mediated cytolysis.

Adenocarcinoma↗

PubMed1994

Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic antigen-presenting cells.

Resting microglia comprise up to 13% of the cells in human central nervous system (CNS) white matter. Their large number and dendritic morphology make them ideally suited to survey the CNS for noxious stimuli. Upon activation microglia gradually lose dendritic processes and transform into typical phagocytic macrophages. Microglia have been implicated as the main antigen presenting cell within the CNS, and appear to be of central importance as effectors and regulators of demyelination. To further characterize the capacity for immune reactivity within the human CNS, we have studied several characteristics of microglia, both in situ and in vitro. We find that human microglia have ultrastructural, phenotypic (CD11c, CD68, acid phosphatase), and functional (FcR and CR mediated phagocytosis) properties typical for cells of the monocyte lineage. Our data indicate that microglia also have properties in common with dendritic antigen-presenting cells. Electron microscopy studies show extended dendritic cell processes on cultured microglia, and microglia are, like dendritic cells, negative for the monocyte markers nonspecific esterase, endogenous peroxidase, CD14, and RFD7. Microglia constitutively express HLA-DR in situ, and express the dendritic cell marker RFD1 upon activation. Coculturing of microglia with CD4+ T cells results in clustering of T cells around microglia and initiation of a mixed lymphocyte reaction, both distinguishing features of dendritic cells. These functional properties of microglia may be of importance for the maintenance of an immunologic response in the CNS, an organ where dendritic cells, in contrast to other organs, have not previously been identified.

Adult↗

PubMed1994

Reactive microglia in multiple sclerosis lesions have an increased expression of receptors for the Fc part of IgG.

Receptors for the Fc part of IgG, FcRI (CD64), FcRII (CD32), and FcRIII (CD16) were studied by indirect immunoperoxidase staining of cryostat sections from normal and multiple sclerosis (MS) brains. Microglia in the parenchyma of normal white matter had a dendritic morphology, and were weakly stained by monoclonal antibodies (mAbs) to FcRI, FcRII, and FcRIII. In active MS lesions reactive microglia were strongly stained by the mAbs 32.2 (FcRI), IV-3 (FcRII), and 3G8 (FcRIII). Perivascular macrophages were stained by all anti-FcR mAbs in both normal white matter and in MS lesions, whereas endothelial cells were stained by the anti-FcRIII mAb only. The FcR on microglia and perivascular macrophages may be of functional importance in antibody-dependent cell-mediated cytotoxicity (ADCC), phagocytosis, and local immunoregulation. FcR on endothelium may be of importance in binding and transportation of immune complexes into the CNS. FcR mediated functions may consequently be highly relevant to the pathogenesis of MS.

Adult↗

PubMed1994

Fc receptor for IgG (FcR) on rat microglia.

Receptor for IgG (FcR) was demonstrated on rat microglia in vivo and in vitro by immunohistochemical staining with immune complexes of horseradish peroxidase (HRP) and rabbit IgG anti-HRP. Astrocytes, oligodendrocytes and neurons did not express FcR. Microglia in culture also showed FcR-mediated agglutination and phagocytosis of IgG-sensitized erythrocytes. A radiolabelled cDNA probe for rat FcRIII hybridized with a 1.4-kb RNA band in Northern blots prepared from total RNA from rat brain. FcRIII mRNA-positive cells in rat brain, presumably microglia, were demonstrated by in situ hybridization. FcR participates in the initiation of cytotoxic responses and of phagocytosis by microglia and is therefore likely to be important in mediating immune reactions in the brain.

Animals↗