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B Dugas

Publications and source records attributed to B Dugas.

At least 73 records · Page 4Linked to original sources
PubMed1993

Functional interaction between beta 2-adrenoceptor agonists and interleukin-4 in the regulation of CD23 expression and release and IgE production in human.

Normal human peripheral blood mononuclear cells (PBMC) produced IgE when stimulated with IL-4. In the present report it was shown that beta 2-adrenoceptor agonists, salbutamol and fenoterol, potentiated the IL-4-induced IgE production without significantly affecting the expression of the low affinity receptor for IgE at the cell surface of monocytes and B lymphocytes. However, beta 2-adrenoceptor agonists were shown to enhance at day 7 the IL-4-induced release of the soluble form of CD23 (sCD23) by PBMC. This effect was specific since a beta-adrenoceptor antagonist, D,L-propranolol, inhibited the IL-4-induced IgE production by these cells. Alternatively, the beta 2-adrenoceptor agonists inhibited the production by these cells of interferon-gamma (IFN-gamma) but did not affect the production of IL-4 when stimulated with phytohemagglutinin A + a phorbol ester. These data suggest that beta 2-adrenoceptor agonists influence the IL-4-induced IgE production in humans by enhancing the release of sCD23 and inhibiting the production of endogenous IFN-gamma. In addition to the effect on the IL-4-induced IgE production it was shown that beta 2-adrenoceptor agonists potentiated the effect of IL-4 on a human promonocytic cell line, U 937, by enhancing CD23 expression and release and by inducing the differentiation of these cells into monocyte-like cells. Taken together, these data indicate that beta 2-adrenoceptor agonists potentiated the effect of IL-4 and that this functional interaction is different considering the cell-lineage and the stage of differentiation of these cells.

Adrenergic beta-Agonists↗
PubMed1993

Maturation of human myelomonocytic leukemia cells following ligation of the low affinity receptor for IgE (Fc epsilon RII/CD23).

The regulation of the low affinity receptor for IgE (Fc epsilon RII/CD23) expression and its role were investigated in U937 cell line and in leukemic cells from a patient (Amb) with acute myeloblastic leukemia. Both cell populations were CD23- but could acquire CD23 expression following treatment with IL-4. CD23+ cells, however, remained blastic and did not show any significant phenotypical and functional modifications. Following ligation of the CD23 on U937 and Amb cells by anti-CD23 mAb, these leukemic cells differentiated into mature monocyte/macrophage-like cells. CD23 ligation promoted the expression of the monocyte marker, CD14, increased the expression of the common beta chain of the LFA-1 family (CD18), and down-regulated the expression of the promonocytic marker CD33. Morphological and phenotypical changes were associated with functional modifications as CD23 ligation allowed the acquisition of the oxidative metabolism in leukemic cells as revealed by luminol-dependent chemiluminescence. As in mature monocytes, CD23 ligation induced an accumulation of intracellular cAMP in leukemic cells. These data indicate that ligation of CD23 may induce the maturation of myelomonocytic cells into monocytic-like cells.

Cyclic AMP↗
PubMed1993

Beta 2-adrenoceptor stimulation augments the IL-4-induced CD23 expression and release and the expression of differentiation markers (CD14, CD18) by the human monocytic cell line, U 937.

The effect of beta 2-adrenoceptor agonists and interleukin-4 (IL-4) on the CD23 expression on, and release from, the human promonocytic cell line, U 937, was investigated. As assessed by flow cytometry, incubation of U 937 cells in the presence of salbutamol, fenoterol or IL-4 induced a concentration- and time-dependent increase in CD23 expression, that was maximal after 48 hr and followed by a decrease thereafter. In addition, salbutamol potentiated the effect of IL-4, the optimal concentration of the drug being a function of the concentration of this cytokine. This synergy between IL-4 and beta 2-adrenoceptor agonists was also observed for the release of the soluble form of CD23. The effect on CD23 expression of salbutamol and fenoterol, but not of IL-4, was blocked in the presence of D,L-propranolol (1 microM) or butoxamine (1 microM). The alpha-adrenoceptor agonist, norepinephrine (1 microM), was ineffective in inducing CD23 expression or potentiating the one evoked by IL-4. Salbutamol down-regulated the expression of Fc gamma RI (CD64) and Fc gamma RII (CD32) whereas IL-4 was ineffective. Only when added together at the onset of the culture did salbutamol and IL-4 induce, after 48 hr, the expression of the monocyte marker, CD14. The expression of CD18 was up-regulated in response to salbutamol either alone or in combination with IL-4, this cytokine alone being inefficient. These data suggest that IL-4 and beta 2-adrenoceptor agonists induce differentiation of U 937 cells into monocyte-like cells.

Adrenergic beta-Agonists↗
PubMed1993

Purification of normal human bone-marrow-derived basophils.

It is well established that basophils and eosinophils share a common differentiation pathway, although the factors regulating their terminal commitment (towards one or other lineage) are not yet fully defined. Interleukin-3 (IL-3) is a major differentiation factor for both human eosinophils and basophils, yielding a mixed population composed predominantly of eosinophilic cells (65 +/- 9%; n = 4), basophils at different stages of maturity (29 +/- 6%; n = 4) and monocytes/macrophages (6 +/- 3%; n = 4), after 3-4 weeks in culture. Using a relatively rapid and simple method involving a first step of gradient density centrifugation over a Percoll gradient (d = 1.063 g/ml) and a subsequent step of adhesion on tissue-culture-treated plastic, a cell population composed of 94 +/- 5% normal basophils and their precursors, with no demonstrable mast cells, was reproducibly obtained from human hematopoietic cells cultured for 3-4 weeks in the presence of recombinant IL-3. These cells contained high levels of histamine (1.39 +/- 0.14 pg/cell) and released this mediator upon stimulation with calcium ionophore A23187 and in a dose dependent manner upon stimulation with IgE-anti IgE, demonstrating their functional capacity. This relatively simple method therefore permits the production of large quantities of pure populations of normal and functional human bone-marrow-derived-basophils.

Basophils↗
PubMed1993

Biochemical and functional alterations induced by CD23 ligation in the human promonocytic cell line U937.

The early events triggered in interleukin-4 (IL-4)-stimulated U937 cells by ligation of CD23/Fc epsilon RII with specific monoclonal antibodies (mAb) were analysed, as a model of the action of this molecule on the differentiation of promonocytic cells. As well as IL-4-activated human monocytes, addition of anti-CD23 mAb to IL-4-treated U937 cells triggered cAMP accumulation but did not evoke significant polyphosphoinositide hydrolysis. However, by a microspectrofluorometric technique allowing single cell analysis, anti-CD23 mAb was found to elicit calcium mobilization in these cells. In addition, the treatment induced phenotypic alterations in these cells, as evidenced by the acquisition of the monocyte marker CD14 and the increase of the alpha-chain (CD11a) and of the common beta-chain (CD18) of the leucocyte function-associated antigen 1 (LFA-1) family antigens. Although weaker than in monocytes, CD23 ligation evoked a small secretion of the pro-inflammatory mediators IL-6 and thromboxane B2. These data suggest that a significant maturation of promonocytic cells towards a more mature monocytic phenotype can be achieved through successive exposure to IL-4 and CD23 ligation.

Antibodies, Monoclonal↗
PubMed1993

Functional interaction between interleukin-9/P40 and interleukin-4 in the induction of IgE production by normal human B lymphocytes.

Interleukin-4 (IL-4) has been shown to induce a high rate of IgE production by normal B lymphocytes from peripheral blood without preactivation of these cells. In the present study, significant IgE production was observed at the concentration of 30 U/mL IL-4 (0.5 ng IgE/mL), and a plateau value was reached at 300 U/mL (1.2 ng IgE/mL). In these experiments, recombinant human (rh) and murine (rm) interleukin-9/P40 (IL-9/P40) were unable to induce such an IgE production by human B lymphocytes. However, in the presence of a suboptimal dose of IL-4 (100 U/mL), both rh and rm IL-9/P40 enhanced the IgE production in a dose-dependent manner (from 3 to 1000 U/mL). Under these experimental conditions, the slight but significant (p < 0.01, Student's t test) production of IgG (50 ng/mL) was also potentiated when the cell cultures were performed in the presence of 300 U/mL of IL-9/P40. The IL-4-induced IgG and IgM production by purified B lymphocytes preactivated with Staphylococcus aureus Cowan strain I was also potentiated in the presence of 300 U/mL of rh IL-9/P40, indicating a direct effect of this cytokine on this cell type. In contrast, IgE production by Staphylococcus aureus Cowan strain I-activated B lymphocytes was never observed. Taken together these data suggested a direct role for IL-9/P40 in the regulation of immunoglobulin production by B lymphocytes.

Animals↗
PubMed1993

Interleukin-9 potentiates the interleukin-4-induced IgE and IgG1 release from murine B lymphocytes.

Interleukin-9 (IL-9) is a mouse T-cell-derived cytokine that supports the growth of mucosal type mast cells suggesting its role in the regulation of type I hypersensitivity reactions. Therefore the possible effect of IL-9 on the in vitro regulation of IL-4-induced IgE and IgG1 releases in the mouse was investigated. In this report, we present evidence that IL-9 potentiated IL-4-induced IgE and IgG1 releases from lipopolysaccharide (LPS)-primed murine B lymphocytes, whereas IL-9 alone was ineffective. The potentiating effect of IL-9 is specific for IgE and IgG1 since no effect on IgM production was observed. This potentiating effect was neither related to an enhanced cell viability, nor to an alteration of the IL-4-induced expression of class II antigens by murine B cells. Besides the fact that IL-9 increased the number of IgG1-secreting cells, this cytokine might also enhance immunoglobulin release on a cell basis. Taken together, these data suggest that IL-9 plays an in vitro regulatory role in antibody synthesis, probably via a direct action on murine B lymphocytes.

Animals↗
PubMed1993

[Immunomodulatory and anti-oxidant effects of bovine lactoferrin in man].

Lf presented differential effects in the induction of normal human monocyte activation. Lf inhibits the free radical generation by normal human monocytes in response to PMA. This effect on free radical generation is linked to the nature of the divalent cationic metal that substitutes the Apo-Lf. Indeed, the substitution of Fe2+ by another cationic transition metal (Cu2+, Zn2+, Pt2+ or Au2+) modifies the anti-oxidant effect of Lf. Among the different substituted Lf the Lf saturated with Cu2+ is the more potent inhibitor of free radical generation by normal human monocytes. In addition to its anti-oxidant effect, Lf stimulates, in combination with LPS, the production of cytokines (IL-1 beta, TNF-alpha and IL-6) and of prostacyclin (PGI2) by normal human monocytes. This potentiating effect is independent of the cation that substitutes the Lf, since the Apo-Lf is able to induce such a potentiating effect. In addition, whereas Lf does not modulate the phenotype of normal human monocytes stimulated or not with IL-4 it does enhance the IL-4-induced release of the soluble form of CD23 by these cells.

Adjuvants, Immunologic↗
PubMed1992

Ligation of CD23 triggers cAMP generation and release of inflammatory mediators in human monocytes.

Transduction through the CD23 molecule (Fc epsilon RII) was analyzed in normal human monocytes using monoclonal antibodies to CD23 (MHM6 and 135) and IgE/anti-IgE immune complexes. Monocytes expressing an increased amount of CD23 molecules were obtained by stimulation with IL-4 (30 U/ml). Anti-CD23 mAb as well as IgE/anti-IgE immune complexes were unable to induce any significant calcium mobilization [Ca2+]i in CD23-bearing monocytes whereas they elicited [Ca2+]i increase in B lymphocytes of the same donors. Despite their failure to induce calcium mobilization, the same CD23 ligands triggered a dose-dependent increase of intracellular cAMP, with a maximum 20 to 30 min after the onset of stimulation. This effect is mediated via CD23 inasmuch as: 1) F(ab)'2 fragments are as active as intact anti-CD23 mAb and 2) it is not observed in CD23- monocytes. The increase in cAMP was only partially altered in the presence of 1 microM indomethacin suggesting that it was not due to the release of PG. The possible role of CD23 in the activation of human monocytes was next documented by showing that anti-CD23 mAb and IgE/anti-IgE immune complexes induced the generation of IL-6 and of thromboxane B2 by CD23+ but not by CD23- monocytes. In addition, the IgE/anti-IgE-induced IL-6 production was potentiated in the presence of cAMP inducer such as the beta 2-adrenoceptor agonist salbutamol. These results indicate that ligation of CD23 induces cAMP generation in CD23+ human monocytes and that CD23 may regulate the IgE-dependent functions in normal human monocytes.

Acute-Phase Reaction↗
PubMed1991

Effect of bacterial toxins on human B cell activation. II. Mitogenic activity of the B subunit of cholera toxin.

The B subunit of cholera toxin (CT) but not the entire CT was found to induce the proliferation of resting human B lymphocytes. A significant mitogenic effect was observed for B subunit concentrations greater than 1 microgram/ml and reached a maximum of stimulation at 10 micrograms/ml. As already described for B lymphocytes preactivated with Staphylococcus aureus Cowan Strain I (SAC). B lymphocytes preactivated with the B subunit of CT, but not with the entire CT, were able to proliferate in response to exogenous interleukin 2 (IL 2) and to the low-molecular weight B cell growth factor (BCGF). To determine the transmembrane signaling system used by the B subunit of CT to mediate its biological effects, we compared the transmembrane signals used by the entire CT, its B subunit and SAC. In comparison to the entire CT, which directly activates adenylate cyclase and increases intracellular cAMP levels, neither the B subunit nor SAC modified the cAMP content. In contrast, although SAC induced inositol phosphate generation neither CT nor the separate subunits were able to induce such a production. Moreover, changes in the fluorescence of indo-1-loaded B lymphocytes revealed that mitogenic doses of either the B subunit or SAC induced a rapid and sustained increase in cytoplasmic free Ca2+ concentration ([Ca2+]i). The effect of the B subunit appeared to be largely dependent on the presence of extracellular Ca2+, because in Ca2(+)-free medium no [Ca2+]i uptake was observed. In contrast, the SAC-induced [Ca2+]i uptake is substantially, but not totally, inhibited in Ca2(+)-free medium, suggesting that part of the rise in [Ca2+]i was due to the release from internal stores. Moreover, fluorimetric measurements on loaded cells with 2',7'-bis(carboxyethyl)-5(6')-carboxyfluorescein revealed that SAC induced a rapid cytoplasmic alkalinization via activation of Na+/H+ exchange, whereas the entire CT and its B subunit had no effect on intracellular pH. Taken together, these data suggest that, in comparison to SAC, the mitogenic effect of the B subunit of CT was mediated through different intracellular biochemical pathways.

B-Lymphocytes↗
PubMed1991

Role of interferon-gamma on the in vivo expression of functional interleukin-2 receptors by murine macrophages.

Interferon-gamma activates both in vitro and in vivo macrophage functions. Injection of rat recombinant interferon-gamma (rR-IFN-gamma) induced the expression of interleukin-2 receptors (IL-2R) by peritoneal macrophages from normal BALB/c and MRL-+/+ mice. Moreover, rR-IFN-gamma stimulated in a dose-dependent manner the oxidative burst of cells as revealed by luminol-dependent chemiluminescene (LDCL). Resident peritoneal macrophages from MRL-lpr/lpr (mice that develop a systemic lupus-like syndrome) showed a higher PMA-triggered LDCL response. This enhanced activity was accompanied by an increase in IL-2R expression (30% vs. less than 1%). The "activated" macrophages from rR-IFN-gamma-treated normal mice as well as MRL-lpr/lpr mice did not respond to the addition of recombinant interleukin-2 (rHu-IL-2) by an increase in LDCL. However, rHu-IL-2 triggering became efficient when cells enriched in IL-2R-bearing macrophages were preincubated overnight with rHu-IL-2R. This response may point out a functional role for IL-2R and provide a role for IL-2 in certain macrophage functions.

Age Factors↗
PubMed1991

Activation of guinea pig alveolar macrophages by endothelin-1.

Endothelin-1 (ET-1) induced a concentration- and time-dependent increase in arachidonic acid release from guinea pig alveolar macrophages, a maximum being reached at 1 nM ET-1. Regarding the time-course study, maximal release of arachidonic acid was observed after 30 s of incubation with ET-1 and then followed by a marked decrease, suggesting a reuptake of free arachidonic acid. ET-1 (0.1-10 nM) induced a concentration- and time-dependent release of TXB2, the stable metabolite of TXA2, evaluated by an ELISA technique. Maximum release was also obtained with 1 nM ET-1 but only after a 1-min incubation period. By contrast, ET-1 (1 pM-1 microM) did not stimulate the release of superoxide anion at any time point of the kinetic study. These results suggests that ET-1 may activate guinea pig alveolar macrophages, probably through a mechanism involving the arachidonic acid pathway.

Animals↗
PubMed1991

Beta-2-adrenoceptor agonists up-regulate the in vitro Fc epsilon receptor II/CD23 expression on, and release from, the promonocytic cell line U937 and human blood monocytes.

The possible regulatory role of beta 2-adrenoceptor agonists in the modulation of CD23 on the human promonocytic cell line U937 and on human monocytes was investigated. Incubation for 48 h in the presence of interleukin-4 (IL-4; 30 U/ml) induced optimal expression and release of CD23 on both U937 cells and human monocytes. When a beta 2-adrenoceptor agonist, either salbutamol or fenoterol, was added to U937 cells or monocytes both the IL-4-induced CD23 expression and release were markedly up-regulated. This effect was dose-dependent, starting at 10 nM and reaching a maximum at 1 microM final concentration of either salbutamol or fenoterol. The potentiating effect of salbutamol and fenoterol on CD23 expression and release was not observed when a beta-adrenoceptor antagonist, either D,L-propranolol (1 microM) or butoxamine (1 microM), was added to the incubation medium. The alpha-adrenoceptor agonist norepinephrine (1 microM) was ineffective in enhancing the IL-4-induced expression and release of CD23 from U937 cells or human monocytes, demonstrating the specificity of the beta 2-adrenoceptor-mediated effect. In the absence of IL-4, a moderate but significant increase in the CD23 expression on U937 cells and human monocytes by these drugs was observed, as compared to the basal values. These results indicate that, besides their bronchodilator effect, beta 2-adrenoceptor agonists may regulate IgE-dependent processes.

Adrenergic beta-Agonists↗
PubMed1991

Pharmacological modulation of the antigen-induced expression of the low-affinity IgE receptor (Fc epsilon RII/CD23) on rat alveolar macrophages.

Brown-Norway (BN) rats were sensitized by 3 aerosol exposures to ovalbumin (OA; 10 mg/ml) at days 1, 3 and 14. At day 21, the rats were challenged with the antigen or vehicle by aerosol. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and the expression of Fc epsilon RII/CD23 was assessed by flow cytometry after staining with the BB10 monoclonal antibody. A maximum of 74% of the AM from sensitized and challenged BN rats expressed FC epsilon RII/CD23 24 h after OA exposure, compared to 12% of the cells from rats exposed to vehicle. Sprague-Dawley rats were passively sensitized by intravenous injection of 0.1 or 0.05 ml/kg mouse ascitic fluid containing dinitrophenyl (DNP)-specific monoclonal IgE (2682-1) and after 24 h exposed to an aerosol of 5 mg/ml of DNP-bovine serum albumin for 30 min. In this case also, antigen exposure induced the expression of Fc epsilon RII/CD23 on 75% AM, compared to 17% AM from saline-challenged rats. Such an induction of Fc epsilon RII/CD23 on AM was, however, not observed when the animals were challenged with either histamine, serotonin or acetylcholine by aerosol. The antigen-induced expression of Fc epsilon RII/CD23 on AM was inhibited upon treatment of the rats with ketotifen or beclomethasone. In addition, oral or aerosol administration of respectively BN 50730 or BN 52021 (two structurally unrelated platelet-activating factor antagonists), inhibited the antigen-induced Fc epsilon RII/CD23 expression on AM, indicating the participation of this lipid mediator in this process.

Animals↗