References of "Heinen, Ernst"
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See detailThe mouse lymph organs
Heinen, Ernst ULg; Defresne, M. P.

in "Handbook of Vertebrate Immunology (1998)

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See detailDemonstration of the expression of CD95 ligand transcript and protein in human placenta
Zorzi, Willy ULg; Thellin, Olivier ULg; Coumans, Bernard ULg et al

in Placenta (1998), 19(4), 269-277

Tolerance of the fetal allograft enables the human conceptus to implant itself into the maternal uterus and survive and grow there. This tolerance phenomenon remains largely obscure, notably because it ... [more ▼]

Tolerance of the fetal allograft enables the human conceptus to implant itself into the maternal uterus and survive and grow there. This tolerance phenomenon remains largely obscure, notably because it appears to be controlled by multiple mechanisms. CD95 ligand (CD95-L), which can trigger death of CD95-positive cells by apoptosis, may participate in inducing anti-fetus-sensitized CD95-positive T lymphocytes to enter apoptosis. Using immunohistochemistry (first trimester and term placentae), FAGS assays (term placenta) and RT-PCR assays (term placenta), the presence of CD95-L protein and mRNA has been shown in crude placental tissue preparations and isolated placental cells. Among the latter, CD95-L expression was detected in trophoblastic cells, fetal blood cells (mRNA only) and also the Hofbauer macrophages. No CD95-L was detected in fibroblasts or fetal endothelial cells. Thus trophoblastic cells, Hofbauer macrophages, and perhaps also fetal blood cells could form a sequential barrier blocking maternal activated defence cells bearing CD95 molecules. (C) 1998 W. B. Saunders Company Ltd. [less ▲]

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See detailBoth Pituitary and Placental Growth Hormone Transcripts Are Expressed in Human Peripheral Blood Mononuclear Cells (Pbmc)
Melen-Lamalle, Laurence ULg; Hennen, Georges ULg; Dullaart, R. P. et al

in Clinical & Experimental Immunology (1997), 110(2), 336-40

The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered ... [more ▼]

The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered to be exclusively expressed in human placenta, where it replaces maternal circulating hGH-N at the end of pregnancy. In this study we investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis hGH-N, and hGH-V, gene expression in PBMC in men, women and pregnant women. We have demonstrated that hGH-N and hGH-V transcripts are simultaneously produced by PBMC in both men and women as well as pregnant women. The PBMC of a PIT-1-negative woman expressed only the hGH-V transcript, but not the hGH-N one as expected. In conclusion, hGH-V mRNA is expressed by cells other than the syncytiotrophoblast, is not regulated by PIT-1, and may be involved in immune regulation, as is pituitary GH. [less ▲]

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See detailThe Placental Growth Hormone is Biologically Active
Thellin, Olivier ULg; Coumans, Bernard ULg; Zorzi, Willy ULg et al

Conference (1997, October)

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See detailThe Expression of the Pituitary Growth Hormone Receptors by Blood Mononuclear Cells Can Be Modulated
Coumans, Bernard ULg; Thellin, Olivier ULg; Zorzi, Willy ULg et al

Poster (1997)

The action of the human pituitary growth hormone has been recently revealed in addition to its traditionnal effects on the staturo-ponderal growth and on the lipid and carbohydrate metabolism. We ... [more ▼]

The action of the human pituitary growth hormone has been recently revealed in addition to its traditionnal effects on the staturo-ponderal growth and on the lipid and carbohydrate metabolism. We demonstrated the presence of hGH-N receptors by cytometry in various peripheral mononuclear blood cells. These hGH-N-R were detected on B lymphocytes and on monocytes, contrarily to the T cells which were mostly negative. Since most blood cells are in a quiescent state, we have tested hGH-N-R expression by stimulated cultured blood cells. After PHA-L activation, most of T cells did express hGH-N-R. After SAC stimulation, B cells continue to express hGH-N-R. Monocytes can be induced to enhance the hGH-N-R expression. Since lymphocyte activation requires antigen recognition and costimulatory signals given by accessory or lymphoid cells, we can now hypothesise that activated cells bear higher numbers of certain receptors rendering them particularly receptive to messages, such as growth hormone, from the neuro-endocrine system. Quiescent B cells appear more sensitive to growth hormone signalling than T cells, but activation open the latter to the influence of growth hormone. The sensitivity of the immune system to signals of the neuro-endocrine system thus depends on its stimulation level. These observations reinforce the view that hGH-N is part of the immune system regulation machinery. [less ▲]

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See detailThe Placental Growth Hormone is Biologically Active
Thellin, Olivier ULg; Coumans, Bernard ULg; Zorzi, Willy ULg et al

Poster (1997)

The human pituitary growth hormone (hGH-N) acts on the staturo-ponderal growth and on the lipid and carbohydrate metabolism but also appears to play a part in the regulation of the immune system. During ... [more ▼]

The human pituitary growth hormone (hGH-N) acts on the staturo-ponderal growth and on the lipid and carbohydrate metabolism but also appears to play a part in the regulation of the immune system. During human pregnancy, the maternal blood concentration of hGH-N decreases whereas that of the placental growth hormone (hGH-V) produced by trophoblastic cells increases. Interestingly, lymphoid cells are able to produce hGH-N and hGH-V and express hGH-N receptors. Here it appears that lymphoid cells can possess hGH-V receptors. The question is thus to know if hGH-V exerts the same effects as hGH-N on the immune system. In this study, we demonstrate that hGH-V, like hGH-N, is able to promote the proliferation of the IM-9 B cell line. We also observed that hGH-V modulates the proliferation capacity of JEG-3 cells, a choriocarcinoma cell line, which is insensitive to the action of hGH-N. Thus one can suspect a retroaction of hGH-V on the trophoblastic cells. [less ▲]

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See detailIn vivo behavior of poly(D,L)-lactide microspheres designed for chemoembolization
Flandroy, P.; Grandfils, Christian ULg; Danen, B. et al

in Journal of Controlled Release (1997), 44(2-3), 153-170

Although chemoembolization advantageously combines arterial embolization of the vascular supply of a neoplasm with controlled intra-arterial infusion of chemotherapeutic drug(s), its application is ... [more ▼]

Although chemoembolization advantageously combines arterial embolization of the vascular supply of a neoplasm with controlled intra-arterial infusion of chemotherapeutic drug(s), its application is limited by the lack of appropriate and reliable embolization materials. Recently, calibrated microspheres of poly(D,L)-lactide have proved to be promising in embolization. Nevertheless, repetitive chemoembolization requires the availability of microspheres degradable within a few days. For this purpose, microspheres consisting of a blend of two polyesters of a very different molecular weight (Mn =65 000 and 3500 in a 16:84 wt. ratio) have been prepared and injected in the renal arteries of rabbits. The in vivo fate of these two component microspheres has been compared by radiology and histology to microspheres prepared from the high molecular weight poly(D,L)-lactide. Furthermore, the in vivo degradation of the polymer has been measured by size exclusion chromatography after quantitative reextraction from the embolized kidney. Degradation kinetics has been compared to data previously reported in vitro. According to the observations performed during the in vivo study, the 50/50 microspheres appear more useful for the chemoembolization of tumors. [less ▲]

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See detailHuman follicular dendritic cells in vitro and follicular dendritic-cell-like cells.
Tsunoda, R.; Bosseloir, A.; Onozaki, K. et al

in Cell & Tissue Research (1997), 288(2), 381-9

Human follicular dendritic cell (FDC)-like cells (FLC) have been utilized for the in vitro analysis of germinal center reactions. However, there is no consensus whether FLC represent FDC in vitro. The ... [more ▼]

Human follicular dendritic cell (FDC)-like cells (FLC) have been utilized for the in vitro analysis of germinal center reactions. However, there is no consensus whether FLC represent FDC in vitro. The purpose of the present study has therefore been to determine distinguishing features of FDC and FLC in vitro. The expression of CD40, CD54, CD49d, cytokine (gamma-IFN and IL-4)-dependent MHC-class II, and CD106 was observed to be specific for the determination of FDC in long-term culture. The cytokine-dependent emperipolesis of germinal center B cells was establised as another discriminating property for FDC in vitro. In 2 out of 72 long-term cultures of FDC, we encountered dividing cells among the non-dividing population of FDC. The dividing cells expressed accessory molecules similar to those of FDC but showed emperipolesis only for the initial few days of their growth. FDC did not enhance the CD40-dependent proliferation of germinal center B cells; in contrast, FLC augumented it. Both types of cells produced a significant amount of cytokine-dependent IL-6. Further studies are needed to determine whether FLC originate from FDC in vitro. [less ▲]

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See detailIn Vitro and in Vivo Stimulation of the Murine Immune System by Agm-1470, a Potent Angiogenesis Inhibitor
Antoine, Nadine ULg; Daukandt, M.; Heinen, Ernst ULg et al

in American Journal of Pathology (1996), 148(2), 393-8

AGM-1470, a potent angiogenesis inhibitor, is already engaged in phase I clinical trials because of its effectiveness to restrain tumor growth and its lack of major side effects. Recently, we showed that ... [more ▼]

AGM-1470, a potent angiogenesis inhibitor, is already engaged in phase I clinical trials because of its effectiveness to restrain tumor growth and its lack of major side effects. Recently, we showed that AGM-1470 stimulates in vitro human B lymphocyte proliferation through T lymphocytes. These data prompted us to explore the in vivo effects of AGM-1470 on the immune system in a mouse model. In this study, we showed that AGM-1470, in synergy with phytohemagglutinin, stimulates the proliferation of murine lymphocytes isolated from lymph nodes. This effect was similar to the one observed with human lymphocytes. When injected subcutaneously or intraperitoneally into mice at pharmacological doses, AGM-1470 induced a significant increase of axillary and mesenteric lymph nodes, respectively. Histological and morphological analyses showed that this phenomenon is mostly due to a hyperplasia of the germinal centers. On average, the area of the germinal center of lymph nodes from AGM-1470-treated mice were three times larger than in lymph nodes from control mice. Interestingly, no effect was observed when AGM-1470 was injected subcutaneously into T-deficient nude mice. Our data demonstrate that AGM-1470 stimulates B cell proliferation in vivo as suggested by the in vitro experiments. This effect should be taken into account in the follow-up of patients treated with this molecule and calls for additional studies to determine the biological consequences of such a stimulation on the host immune system. [less ▲]

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See detailRegulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo.
De Smedt, T.; Pajak, B.; Muraille, E. et al

in Journal of Experimental Medicine (1996), 184(4), 1413-24

Dendritic cells (DC) are described as "nature's adjuvant," since they have the capacity to sensitize T cells in vivo upon first encounter with the antigen. The potent accessory properties of DC appear to ... [more ▼]

Dendritic cells (DC) are described as "nature's adjuvant," since they have the capacity to sensitize T cells in vivo upon first encounter with the antigen. The potent accessory properties of DC appear to develop sequentially. In particular, the ability to process antigens and to sensitize native T cells develops in sequence, a process termed "maturation" that is well described in vitro. Here, we obtain evidence for maturation in vivo in response to the bacterial product lipopolysaccharide (LPS). Before LPS treatment, many DC are found at the margin between the red and white pulp. These cells lack the M342 and DEC-205 markers, but process soluble proteins effectively. 6 h after LPS, DC with the M342 and DEC-205 markers are found in increased numbers in the T cell areas. These cells have a reduced capacity to process proteins, but show increases in the B7 costimulator and T cell stimulatory capacity. 48 h after LPS, the number of DC in the spleen is reduced markedly. We interpret these findings to mean that LPS can cause DC in the marginal zone to mature and to migrate into and then out of the T cell areas. [less ▲]

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See detailThe influence of follicular dendritic cells on B-cell proliferation depends on the activation of B cells and the mitogen used.
Bosseloir, A.; Bouzahzah, F.; Defrance, T. H. et al

in Scandinavian Journal of Immunology (1996), 43(1), 23-30

Follicular dendritic cells (FDC) are unique non-lymphoid cells found only in lymph follicles. They play a part in the survival, proliferation and differentiation of B cells. To analyse the influence of ... [more ▼]

Follicular dendritic cells (FDC) are unique non-lymphoid cells found only in lymph follicles. They play a part in the survival, proliferation and differentiation of B cells. To analyse the influence of FDC on B-lymphocyte proliferation, we isolated them from human tonsils on albumin gradients and treated them with mitomycin C to prevent the multiplication of lymphoid cells harboured in their cytoplasmic evaginations. FDC cultured for 12-16 h remained attached to the substrate; non-adherent cells were carefully eliminated by washing. Purified B cells cultured alone or with contaminant-cleared FDC were maintained for 2 days in the presence or absence of various stimulants, after which tritiated thymidine uptake by these cells was measured. In the absence of activators, FDC did not induce B-cell multiplication. B cells cultured in the presence of FDC exhibited increased 3H-TdR uptake when activated with anti-CD40 MoAb, anti-immunoglobulin MoAb or transferrin, but not when stimulated with Staphylococcus aureus strain Cowan I (SAC) at a given concentration. In the latter case, B-cell proliferation clearly decreased. In control cocultures where mitomycin-C-treated non-adherent cells were used instead of FDC in the presence of the different stimulants, no increase in B-cell proliferation was observed. The results suggest that, inside the germinal centres, FDC modulation of B-cell proliferation depends on the activation state of the B cells and on the stimulant encountered. [less ▲]

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See detailChemotaxis-Promoting and Adhesion Properties of Human Tonsillar Follicular Dendritic Cell Clusters
Bouzahzah, F.; Antoine, Nadine ULg; Simar, Léon ULg et al

in Research in Immunology (1996), 147(3, Mar-Apr), 165-73

Lymph follicles are globular and compact due to aggregation of lymphoid cells on follicular dendritic cells (FDC). To probe the mechanisms underlying this accumulation of cells, we analyse here the role ... [more ▼]

Lymph follicles are globular and compact due to aggregation of lymphoid cells on follicular dendritic cells (FDC). To probe the mechanisms underlying this accumulation of cells, we analyse here the role played by FDCs in attracting and binding cells. FDCs prepared from human tonsils by mild separation techniques appeared in the form of clusters (FDC clusters), where, via cytoplasmic extensions, they enveloped lymphoid cells. Using Boyden's chambers, we demonstrated that these FDC clusters produced one or more chemoattractants capable of inducing chemotaxis of lymphoid cells. Supernatants of FDC cluster cultures also exerted a chemotaxis-promoting effect. FDC clusters induced true chemotaxis, not merely chemokinesis due to cell activation. They secreted a substance or substances that stuck to the substrate (a cellulose filter) and thus induced haptotaxis. B as well as T cells were attracted, but B cells apparently required the presence of T cells to respond fully to the chemoattractant(s). Subtypes of B cells (IgD+ and IgD-) and T cells (CD4+, CD8+, CD57+ AND CD57-) were tested and all were attracted. Since purified lymphoid cells did not induce these phenomena, FDCs were suspected to do so. FDCs have been shown to establish contact with lymphoid cells. Here we have determined that CD4+ T cells adhere in greater number to FDC clusters than do CD8+ T cells. We thus propose that FDCs specifically contribute to construction of lymph follicles by attracting and determining their cell composition. [less ▲]

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See detailThe Potent Angioinhibin Agm-1470 Stimulates Normal but Not Human Tumoral Lymphocytes
Antoine, Nadine ULg; Daukandt, M.; Locigno, R. et al

in Tumori (1996), 82(1, Jan-Feb), 27-30

BACKGROUND: AGM-1470 is a newly synthesized molecule developed as an analog of the potent anti-angiogenic fumagillin. Its efficacy in restraining tumor growth in vivo and the absence of major side effects ... [more ▼]

BACKGROUND: AGM-1470 is a newly synthesized molecule developed as an analog of the potent anti-angiogenic fumagillin. Its efficacy in restraining tumor growth in vivo and the absence of major side effects have already led to phase I clinical trials in patients with solid cancers. However, neither the exact mechanisms of action of AGM-1470 nor its effects on the host of normal cells have been extensively studied. Recently, we showed that AGM-1470 enhanced the proliferation of B lymphocytes in the presence of T cells. Since AGM-1470 could potentially be used in patients with lymphoma, it was urgent to test the effect of the molecule on the proliferation of tumor lymphocytes. METHODS: The possible effect of AGM-1470 on the proliferation of normal or tumor lymphocytes was evaluated by thymidine-incorporated assays. Normal T and B lymphocytes were purified from human tonsils. The tumor lymphocytes used in the study were Molt 3, Molt 4 and Jurkatt cell lines for the T lineage and Daudi and Radji cell lines for the B lineage. RESULTS: As shown previously, AGM-1470 stimulates the proliferation of normal B lymphocytes through an action on normal T cells. THe angioinhibin was ineffective ont eh proliferation of both T and B transformed cells. Moreover, in the presence of the drug, tumor T cells co-cultured with normal B lymphocytes did not induce any increase in B cell proliferation, as previously observed with normal T lymphocytes. Inversely, tumor B cells co-cultured with normal T lymphocytes were insensitive to the drug. CONCLUSIONS: Our results demonstrate that AGM-1470 is ineffective on lymphoid tumor cell proliferation and could potentially be safely administered to lymphoma patients. [less ▲]

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See detailSimulation of Human B-Lymphocyte Proliferation by Agm-1470, a Potent Inhibitor of Angiogenesis
Antoine, Nadine ULg; Bours, Vincent ULg; Heinen, Ernst ULg et al

in Journal of the National Cancer Institute (1995), 87(2), 136-9

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See detailExpression of growth hormone receptors by normal or pathological human lymphoid cells.
Thellin, Olivier ULg; Coumans, Bernard ULg; Mélot, France ULg et al

Poster (1995)

The human pituitary growth hormone (hGH-N) is mainly known for its effects on the staturo-ponderal growth and on the lipid and carbohydrate metabolism. It also plays a part in the immune system regulation ... [more ▼]

The human pituitary growth hormone (hGH-N) is mainly known for its effects on the staturo-ponderal growth and on the lipid and carbohydrate metabolism. It also plays a part in the immune system regulation. According to many authors, hGH-N stimulates the proliferation of peripheral blood mononuclear cells or that of tumoral lymphoid cell lines. With the aid of the FACS (Fluorescent-Activated Cell Sorter), we were able to detect hGH-N receptors on various tumoral cell lines : JURKAT (a acute lymphoid leukemia T cell line), DAUDI and RAJI (acute lymphoid leukemia B cell lines). These receptors were nearly absent from quiescent B or T cells prepared from human tonsils but were expressed in culture conditions after activation. [less ▲]

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See detailAdhesion and costimulatory molecules on human FDC in vitro.
Tsunoda, R.; Heinen, Ernst ULg; Imai, Y. et al

in Advances in Experimental Medicine and Biology (1995), 378

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See detailHuman germinal center CD4+CD57+ T cells act differently on B cells than do classical T-helper cells.
Bouzahzah, F.; Bosseloir, A.; Heinen, Ernst ULg et al

in Developmental Immunology (1995), 4(3), 189-97

We have isolated two subtypes of helper T cells from human tonsils: CD4+CD57+ cells, mostly located in the germinal center (GC), and CD4+CD57- cells, distributed through the interfollicular areas but also ... [more ▼]

We have isolated two subtypes of helper T cells from human tonsils: CD4+CD57+ cells, mostly located in the germinal center (GC), and CD4+CD57- cells, distributed through the interfollicular areas but also present in the GC. In a functional study, we have compared the capacities of these T-cell subtypes to stimulate B cells in cocultures. In order to block T-cell proliferation while maintaining their activation level, we pretreated isolated T cells with mitomycin C prior to culture in the presence of B cells and added polyclonal activators such as PHA and Con A, combined or not with IL-2. Contrary to CD4+ CD57- cells, CD4+CD57+ cells did not markedly enhance B-cell proliferation. Even when sIgD.B cells typical of germinal center cells were tested, the CD4+CD57+ cells had no significant effect. This is in accordance with the location of these cells: They mainly occupy the light zones of the GC where few B cells divide. Even when added to preactivated, actively proliferating cells, CD4+CD57 cells failed to modulate B-cell multiplication. On the supernatants of B-cell-T-cell cocultures, we examined by the ELISA technique the effect of T cells on Ig synthesis. Contrary to CD57+ T cells, whose effect was strong, CD57- T cells weakly stimulated Ig synthesis. More IgM than IgG was generally found. Because CD57 antigen is a typical marker of natural killer cells, we tested the cytolytic activity of tonsillar CD4+CD57+ cells on K562 target cells. Unlike NK cells, neither CD4+CD57+ nor CD4+CD57- cells exhibit any cytotoxicity. Thus, germinal center CD4+CD57+ cells are not cytolytic and do not strongly stimulate either B-cell proliferation or Ig secretion. CD4+CD57- cells, however, enhance B-cell proliferation and differentiation, thus acting like the classical helper cells of the T-dependent areas. [less ▲]

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See detailGerminal Center T Cells: Analysis of Their Proliferative Capacity
Bouzahzah, F.; Bosseloir, A.; Heinen, Ernst ULg et al

in Advances in Experimental Medicine and Biology (1995), 378

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