Biomedical subjects

L Le Goff

Publications and source records attributed to L Le Goff.

36 records · Page 2Linked to original sources

PubMed1994

Involvement of Fc epsilon RII/CD23 and L-arginine dependent pathway in IgE-mediated activation of human eosinophils.

Eosinophils display various receptors for immunoglobulin E (IgE) including the high affinity receptor for IgE (Fc epsilon RI), CD23 (Fc epsilon RII), and Mac-2/epsilon BP. We attempted here to clarify the role of these receptors in IgE-mediated activation of eosinophils from normal human bone marrow cultures. Pretreatment of eosinophils with IL-4 is required for IgE/anti-IgE-mediated stimulation of TNF-alpha and peroxydes production. TNF-alpha release from eosinophils was also induced following ligation of CD23 and to a lesser extent with anti-Mac-2, while Fc epsilon RI-ligation had no effect. IgE/anti-IgE effect dramatically decreased when eosinophils were pretreated with Fab fragments of CD23-mAb. In addition, this effect could also be reversed by inhibiting CD23-dependent nitric oxide pathway by NG-monomethyl-L-arginine. Nitric oxide chemical donor, SIN-1, induced TNF-alpha release from eosinophils. CD23 and nitric oxide pathway are thus involved in IgE-mediated stimulation of normodense human eosinophils.

Antibodies, Monoclonal↗

PubMed1994

Larval biology of six filariae of the sub-family Onchocercinae in a vertebrate host.

The development of six filariae of the sub-family Onchocercinae-Litomosoides sigmodontis, Acanthocheilonema viteae, Molinema dessetae, Monanema martini, Brugia malayi, B. pahangi-was compared in rodents, following a single inoculation of a low or high dose of infective larvae. Analysis was done with 105 rodents dissected and 53 rodents fixed for histopathology. The percentage of larvae which developed corresponded to the proportion of those which were able to penetrate into the sub-cutaneous lymphatic vessels; this percentage was determined during the first day (phase 1) and was characteristic of the filaria-host pair, and independent of the number of larvae inoculated. It could remain stable for a long time, more than eight months with M. martini (phase 2); the phenomena of regulation appeared later (phase 3). The larvae migrated through the lymphatic system, which represents a medium less protected and thus less aggressive than the blood system. The coelomic cavities, almost devoid of inflammatory cells, represented an ultimate shelter, as well as the joint-cavities (colonized by some Dirofilariinae). Localizations in the cardio-pulmonary blood system were accidental and occurred when, during the migrations, some larvae penetrated into the thoracic channel and arrived in the superior vena cava, then the right ventricle and the pulmonary arteries (the biology of Dirofilaria immitis resulted in a secondary adaptation); such accidents may occur with adult filariae, especially, after drug treatment. One may expect similar events in human filariasis. These "occult" filariae, more frequent than it is usually thought, influence the immunological status and the pathology.

Animals↗

PubMed1994

Involvement of cyclic AMP and nitric oxide in immunoglobulin E-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes.

Epidermal keratinocytes (EK) are exposed to multiple inflammatory stimuli and paracrine factors secreted by various dermal cells (lymphocytes, mast cells, macrophages, fibroblasts) during wounding, cutaneous allergy, and infections. We have previously demonstrated that after stimulation with interleukin 4 or interferon-gamma, human EK express the low-affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. In the present study, we showed that the ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal antibody induces a dose-dependent release of interleukin 6 and tumor necrosis factor-alpha from EK. CD23-ligation activates the nitric oxide-dependent pathway, as demonstrated by the high levels of nitrites released in cell supernatants, and the accumulation of intracellular cyclic nucleotides in EK. These second messengers are required for IgE-dependent stimulation of cytokine production by these cells, inasmuch as this is completely abolished by the use of cAMP or nitric oxide synthase antagonists. Human epithelial keratinocytes may thus participate in IgE-mediated immune responses, through their ability to express functional CD23 antigen.

Antibodies, Monoclonal↗

PubMed1994

IgE-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes: the role of cAMP and nitric oxide.

Epidermal keratinocytes (EK) are exposed to multiple inflammatory stimuli and paracrine factors secreted by various dermal cells (lymphocytes, mast-cells, macrophages, fibroblasts) during wounding, cutaneous allergy and infections. We have previously demonstrated that following stimulation with interleukin-4 (IL-4) or interferon-gamma, human EK express the low affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. In the present study, we showed that the ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal antibody, induces a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha from EK. CD23-ligation activates the nitric oxide-dependent pathway, as demonstrated by the high levels of nitrites released in cell supernatants, and the accumulation of intracellular cyclic nucleotides in EK. These second messengers are required for IgE-dependent stimulation of cytokine production by these cells, as this is completely abolished by cAMP or NO synthase antagonists. Human epithelial keratinocytes may thus participate in IgE-mediated immune responses, through their ability to express functional CD23 antigen.

Amino Acid Oxidoreductases↗

PubMed1994

Specific ligation of the HIV-1 viral envelope protein gp120 on human CD34+ bone marrow-derived progenitors.

The precise mechanisms of hematologic abnormalities observed during HIV infection remain unknown. In vitro experiments performed by various authors concerning the HIV toxicity on bone marrow-derived precursors did not allow them to determine whether this toxicity could be mediated through direct or non-direct effects, since it is today unclear if gp120 possesses a direct hematotoxic effect on human bone marrow progenies. The aim of our study was to determine whether labelled gp120 could specifically bind to the membrane of purified human normal CD34+ cells and to investigate the in vitro effect of the gp120 on their growth. To answer these questions, human CD34+ cells were purified from normal bone marrow samples, then labelled with monoclonal antibodies directed either against CD4 antigen or CD34 antigen and/or with FITC labelled gp120 and analyzed by FACS. Our results demonstrate the presence of about 5% of CD4+CD34+ cells and of nearly 12% of CD34+gp120+ precursors. Together with our results concerning the in vitro inhibitory effect of gp120 on the growth of the same purified CD34+ precursors, our data demonstrated the direct hematotoxic activity of HIV-derived gp120 and the possible HIV infection of hematopoietic progenitors through the interaction of gp 120 with CD34+ cell surface.

Antibodies, Monoclonal↗

PubMed1993

IL-4 release by human leukemic and activated normal basophils.

Recently, authors have addressed the ability of human basophils to produce IL-4. We report here the detection of significant serum IL-4 levels in a case of acute transformation of chronic myelogenous leukemia with a predominant basophilic cell population. Leukemic basophils were isolated from patients' PBMC and assayed for their IL-4-mRNA expression and their ability to secrete this cytokine in vitro. Leukemic basophilic cells (> 90% toluidine blue positive) but not other PBMC expressed IL-4-mRNA, contained IL-4 protein, and secreted this cytokine. These cells had a spontaneous IL-4 secretion ability, without a need for an exogenous activator. Meanwhile, IL-4 release was significantly increased following leukemic cell activation through Fc epsilon RI-ligation or by Ca2+ ionophore. IL-4 and its mRNA were also detected in leukemic basophils from three other chronic myelogenous leukemia patients with moderate basophilia (13, 14, and 23% basophils in PBMC). To confirm these data in normal human cells, we have developed a method to obtain large numbers of purified basophils from human bone marrow cell cultures. In contrast to leukemic basophils, normal cells required in vitro activation through Fc epsilon RI ligation or by Ca2+ ionophore to express and secrete IL-4. Leukemic and normal basophils secreted histamine following in vitro activation, but were negative for tryptase. These data thus demonstrate the in vivo and in vitro ability of human basophils to produce IL-4.

Basophils↗

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↗

PubMed1985

The in vitro effects of opines and other compounds on DNAs originating from bacteria, and from healthy and tumorous plant tissues.

Purified total DNAs were isolated from oncogenic or nononcogenic Agrobacterium tumefaciens cells as well as from normal and crown gall tissues. Opines (octopine, nopaline, lysopine), plant hormone (auxin IAA) and some carcinogenic compounds were used in order to correlate their effects on in vitro strand separation and synthesis of DNAs with in vivo tumorous cell multiplication. Octopine (or nopaline) induced chain opening of DNAs originating from octopine (or nopaline)-metabolizing bacteria and from same bacteria strain-induced tumorous cells. This phenomenon was measured by the increase in DNA hyperchromicity which is concentration dependent. The tested compounds stimulated the in vitro synthesis of the same DNAs. Under the same conditions, in vitro strand separation and synthesis of healthy plant DNA was not (or only slightly) enhanced, except in the case of particular hormone-connected healthy cell DNA. IAA and carcinogens stimulated in vitro synthesis and induced in vitro strand separation (dose-dependent effect) of DNAs isolated from crown gall cells and inducing bacteria. Compared to healthy cell DNAs, these DNAs were thus susceptible to structurally very diversified molecules and in this way behave as do mammalian tissue DNAs. The opine and IAA actions observed here were specific for plant tissue DNA; cancerous human or animal tissue DNAs were insensitive. By their presence in the crown gall cells, opines possibly maintain destabilized areas (required for rapid growth and division) on tumor cell DNA. The cooperative actions of IAA and opines as well as small RNA and RNA fragments on gene activation, might explain the autonomy of plant tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1982

In vitro screening of carcinogens using DNA of the His- mutant of Salmonella typhimurium.

Carcinogens: 7,12-dimethylbenz(a)anthracene (DMBA), 2-acetylaminofluorene (AAF), 3-methylcholanthrene (MC), daunorubicin, thio-TEPA, cyclophosphamide, 1-(2-chloroethyl)2-cyclohexyl-1-nitrosourea (CCNU) and mitomycin C, which mutate Salmonella typhimurium tester strains in the Salmonella/microsome mutagenicity test, strongly stimulate the in vitro synthesis of DNA isolated from His- mutants (TA-1538, TA-1537, TA-1535), and induce in vitro His- DNA strand separation. Four other carcinogens, ethionine, actinomycin D, bleomycin and reserpine, which were not known as mutagens in the Ames test, also strongly stimulate His- DNA synthesis and His- DNA strand separation in local areas. Those substances which are neither carcinogenic nor mutagenic: d-lactose, fluorene, cholesterol, and saccharin, do not stimulate either His- DNA (or His+ DNA) synthesis or DNA in vitro strand separation. Steroid hormones, which are carcinogenic only for steroid target tissues, do not react with bacterials DNA.

Animals↗

PubMed1979

[Stimulation of induction or inhibition of crown-gall tumor development by RNA-fragments U2. Interference by auxin].

RNA-fragments U2 obtained by mild degradation with RNase U2 of ribosomal RNA containing A and G nucleotides in excess are capable of exhibiting either a stimulatory effect on the induction of Crown-gall tumors or an inhibitory action on their subsequent development. These different effects are dependent on the moment at which RNA-fragments were introduced into wounded Pea seedlings infected by Agrobacterium tumefaciens B6. The results obtained in vitro and in vivo suggest that an interaction between auxin and RNA-fragments U2 may take place, either increasing the tumor induction or inhibiting the proliferation of tumourous cells.

Cell Transformation, Neoplastic↗

PubMed1976

[A RNA extract from oncogenic and non oncogenic strains of Agrobacterium tumefaciens is an indispensable element for the induction of tumors in Datura stramomium].

An RNA bound to the reverse transcriptase of Agrobacterium tumefaciens has been isolated and shown to be oncogenic for stem tissues of Datura stramonium grown under axenic conditions. The tumorous nature of the cellular change induced by the infectious rna was demonstrated by serial grafts of tumors on Datura stems and by cultivation of tumorous tissue in vitro on a medium without supplemental auxins and cytokinins. Active cellular proliferation within tissues of Datura stems was a prerequisite for expression of the oncogenic potential of the RNA. Further, infectious RNA was isolated from avirulent and attenuated strains of Agrobacterium tumefaciens including attenuated derivatives of strain AC58 which have been "heat-cured" of the plasmid associated with virulence. It is proposed that the infectious RNA is an essential but not the sole component of the tumor-inducing mechanism of the crown-gall bacterium.

Cell-Free System↗

PubMed1975

[Tumorous nature of hyperplasia obtained experimentally].

The determination of the tumorous nature of an overgrowth provides one of the most essential information for all research concerning animal and plant cancerisation. The experimental procedure which will be described here answers to this imperative: it allows to prove the tumorous characteristics of proliferations obtained by inoculation of Agrobacterium tumefaciens RNA fractions to Datura stems.

Cell Transformation, Neoplastic↗

PubMed1972