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F Ouaaz

Publications and source records attributed to F Ouaaz.

28 records · Page 2Linked to original sources
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

[Physiopathological role of low affinity IgE receptor (CD23) in hematopoietic cells].

Ligation of the low affinity IgE receptor by specific monoclonal antibodies or multivalent IgE complexes result in the transduction of signals which differ according to the CD23 isotype expressed by the various cell types. In B lymphocytes, it elicits the early activation of phospholipase C through a mechanism involving a G-protein insensitive to Pertussis toxin, followed by a late phase of cAMP accumulation. In monocytes, which express the CD23b isoform, ligation of CD23 was also found to induce a delayed accumulation of cAMP, that was largely dependent on a prior cGMP increase through a mechanism involving the activation of a NO synthase. This pathway, which appears to be exacerbated in allergic diseases, seems to play an important role in the differentiation of cells of the monocytic lineage, their capacity to release proinflammatory mediators and their cytotoxic functions.

Amino Acid Oxidoreductases↗
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

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

Interleukin 4 inhibits the proliferation and promotes the maturation of human leukemic early B cells.

The effects of interleukin 4 (IL-4) on human leukemic precursor B-cell lines were investigated. Recombinant IL-4 (rIL-4) was added to three acute lymphoblastic leukemia-derived pre B-cell lines: Reh, Km3 and Nalm-6. Our results show that rIL-4 significantly decreases continuous proliferation of Reh and Km3 cells while Nalm-6 cells have a limited response in this respect. This rIL-4 effect is dose-dependent and can be neutralized by anti-IL-4 monoclonal antibody (mAb). Furthermore, rIL-4 down-regulated IL-3-induced proliferation of Reh cells. Phenotypic analysis of rIL-4-treated cells points to significant induction of surface marker maturation of leukemic cells by this cytokine. Together, these in vitro data suggest that IL-4: 1) inhibits the proliferation and 2) promotes the differentiation of certain human leukemic B-cell precursors.

Antigens, Differentiation, B-Lymphocyte↗
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↗
PubMedDate not supplied

Expression of CD23 by human bone marrow stromal cells.

CD23 is a surface antigen expressed by a variety of human hematopoietic cells and shown to display multiple biological functions. In present work, we assayed CD23 expression by human bone marrow (BM) or by stromal cells derived from this tissue. While freshly isolated BM-cells showed low CD23 expression, a subset of long term BM-culture (LTBMC)-derived stromal cells expressed CD23 mRNA at high levels in their steady state and secreted soluble CD23 in their culture supernatants. To assay the role of CD23 in LTBMC, these cultures were initiated in the presence of neutralizing anti-CD23 mAb. A dramatic decrease in total numbers of hematopoietic cells and CFU-GM recovery was observed in these cultures as compared to controls. These data suggest a role of CD23 expression in stroma cell functions and further confirm the ability of this antigen to regulate human hematopoietic cell development.

Antibodies, Monoclonal↗