The role of CD23 on early human hematopoietic precursors.
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Antigens, CD↗
Biomedical subjects
M Arock
Publications and source records attributed to M Arock.
Proliferation of early human myeloid precursors induced by interleukin-1 and recombinant soluble CD23.
Low affinity Fc epsilon receptors (Fc epsilon RII/CD23) or their soluble fragments have various biologic effects on B- and T-cell lineages. In this study, we have assessed the effect of recombinant soluble CD23 (rsCD23) on the proliferation of human bone marrow (BM)-derived myeloid precursors with or without recombinant interleukin-1 (rIL-1) addition. Non-adherent CD2- or CD34+ BM cell subsets were used as target cells. Our results show that rsCD23 in synergy with rIL-1 displays an interleukin-3-like activity as it promotes the proliferation of multipotential marrow precursors. This effect was abolished by anti-CD23 addition to these cultures, but was not affected by anti-IL-3 monoclonal antibody. Furthermore, sequential study indicates that rIL-1 induces bone marrow cell responsiveness to rsCD23.
Antigens, Differentiation, B-Lymphocyte↗
Specific high-affinity receptors for interferon-gamma on mouse bone marrow-derived mast cells: inhibitory effect of interferon-gamma on mast cell precursors.
Cultured mast cells derived from murine bone marrow were investigated for the presence of specific interferon-gamma (IFN-gamma) receptors, and for the effects of IFN-gamma on mast cell proliferation. 125I-labeled recombinant IFN-gamma (125I-Mu-rIFN-gamma) was shown to bind to high-affinity receptors on these cells. Scatchard analysis of binding data indicated the presence of about 500 homogeneous binding sites per cell, with an apparent equilibrium dissociation constant of 3 X 10(-10) M. The binding of 125I-Mu-rIFN-gamma to mast cells was inhibited by unlabeled Mu-rIFN-gamma but not by unlabeled Mu-IFN-alpha/beta. Cross-linking of 125I-Mu-rIFN-gamma to mast cell membrane proteins using a cross-linking agent yielded a predominant complex of 100 +/- 10 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography which most likely represents the IFN-gamma-receptor complex. To assess the biological significance of these receptors, we studied the effects of Mu-rIFN-gamma on mast cell proliferation, which was markedly inhibited in mast cell precursors but not in mature mast cells. These in vitro results are in agreement with the antiproliferative effect of IFN-gamma previously reported for other hematopoietic progenitors, and suggest that IFN-gamma could find its application in the treatment of human systemic mastocytosis.
Animals↗
Alpha-L-fucosidase isoenzyme pattern in hairy cell leukaemia.
alpha-L-Fucosidase isoenzymes pattern in hairy cell leukaemia (HCL) is characterized by the disappearance of the more acidic form when compared to normal lymphocytes. Our data seem to indicate that this profile could not be related to the T or B phenotype because in normal lymphocytes (mainly T), MO cells possessing T markers, as well as lymphocytes from chronic lymphoid leukaemia (CLL) known to exhibit normal-like B phenotypes two alpha-L-fucosidase forms are identified and especially the more acidic one.
Adult↗
Characterisation of enkephalinase (EC 3.4.24.11) activity on various leukemic cells expressing the common acute lymphocytic leukemia antigen (CALLA).
The deduced amino acid sequences of CALLA, a cell surface marker of human acute lymphocytic leukemia, and human enkephalinase (neutral endopeptidase, EC 3.4.24.11) were recently reported to be almost identical. We show that membranes of CALLA+ cells of the REH lymphoblastic cell line as well as blast cells derived from the blood or bone marrow of patients with acute lymphocytic leukemia display high enkephalinase activity. This activity was abrogated by several enkephalinase inhibitors at concentrations closely similar to those required to inhibit pure human enkephalinase. However, these compounds did not significantly modify the rate of REH cell proliferation in vitro. Hence, the functional role, if any, of the high peptidase activity in lymphoblastic cells remains to be established.
Antigens, Differentiation↗
Histamine-releasing activity of endogenous peptides on mast cells derived from different sites and species.
We have examined the cytological and functional characteristics of mast cells grown in tissue culture from the bone marrow of mice and rats and compared them with mast cells isolated from the peritoneal cavity of these animals. In both species, bone marrow-derived mast cells (considered to be a model of mucosal mast cells) have fewer cytoplasmic granules and lower histamine content than peritoneal mast cells. Sprague-Dawley rat peritoneal mast cells were responsive to various endogenous peptides and to compound 48/80. However, peritoneal mast cells isolated from BDF1 mice (a strain widely used to obtain bone marrow-derived mast cells) were not responsive to the same secretagogues. Rat and mouse bone marrow-derived mast cells obtained from Sprague-Dawley rats and BDFI1 mice were also hyporesponsive to calcium ionophore as compared to peritoneal mast cells and unresponsive to compound 48/80 and peptides. Despite the similarity of the functional characteristics of mouse and rat bone marrow-derived mast cells, mouse bone marrow-derived mast cells could not be used as a model of responsiveness to peptides for rat mucosal mast cells because of the differences in responsiveness between the peritoneal mast cells in the two species. Obtention of homogeneous rat bone marrow-derived mast cells may provide a useful tool to study the functional heterogeneity in an intraspecies system since most of our knowledge on mast cell physiology and pharmacology is derived from studies on rat peritoneal mast cells.
Animals↗
[Effect of retinoic acid on the differentiation and growth of murine mastocyte precursors].
In cultures of normal mouse hematopoietic cells containing Interleukin-3 develop cells with many features of mast cells. These cells seem heterogeneous with respect to morphological and biochemical examination. Nevertheless, most of the cells show many granules and a low ability to self-renew. In the present report we describe the development of a blastic cell population, termed mastoblasts, when normal mouse hematopoietic cells are exposed continuously to retinoic acid (RA: 10(-6) to 10(-5) M/l). Using H*3-thymidine incorporation, cell cycle measurement and protein content by flow cytometry, transmission and scanning electron microscopy, we show that these cells seem to be of mast cell lineage but with a high self-renewing capability. So, RA is able to inhibit mast cell differentiation and to provide us a "mastoblastic" population which could be used as a model to study mast cell differentiation.
Animals↗
Murine basophil-mast differentiation: toward optimal conditions for selective growth and maturation of basophil-mast or allied cells.
Recent investigations revealed that basophil-mast cells were related to the hemopoietic system. Strikingly, murine bone marrow showed a singular paucity in cells with basophil-mast features; moreover in clonogenic assays (methylcellulose, agarose) bone marrow was found to be manifestly poor in basophil-mast progenitor cells. Our work brought to light several new facts concerning the culture and differentiation of this cell type: 1 degree pure and mixed mast clones can be derived in large numbers from bone marrow, provided progenitors are cultured in collagen matrix. Up to 1,382 hemopoietic clones were analysed in situ after staining: 30% contained mast cells (34 per 10(5) cells), thus the basophil-mast lineage was one of the most frequent. We concluded that other cloning media were noticeably nonoptimal for the growth and/or maturation of mast cells. We suggested that collagen and the molecular edifices derived from it, both found in variable amounts in the natural mast environments, should play essential roles in mast phenotype expression. 2 Degrees cholera toxin (CT) selectively eradicated nonmast progenies: mast progenitors and mast progenies were resistant. In this way, pure and rapidly expanding mast cell clones were obtained at a frequency never reported before. CT possibly acts both directly, as a stimulator of mast cell proliferation, or indirectly on marrow subpopulations which repress basophil-mast cell growth and maturation. In vitro culture conditions, specifically designed for basophil-mast lineage, should prove of interest in the search for an unifying hypothesis concerning the multiple forms of mast cells found in various tissues.
Animals↗
[Culture of murine mastocytes: heterogeneity of the ultrastructural aspects].
In cultures of normal mouse hematopoietic cells containing mast cell growth factor develop cells with many features of mast cells. These cells seem heterogeneous with respect to size, cell surface, granules maturity and morphology of nucleus using transmission and scanning electron microscopy. Alcian blue-safranin staining shows that most of the proteoglycan synthesized by cultured mast cells is weakly sulfated and non heparin-mucopolysaccharides. These results support the view that cultured mast cells resemble to mucosal mast cells, and are clearly different from serosal mast cells.
Animals↗
[Determination of total nitrogen in biological milieux by chemoluminescence: a comparison with the reference method].
An assay technique for the chemiluminescent estimation of total nitrogen in biological samples have been used for two hundred urines and gastric fluids, and results compared with those given by the traditional Kjeldahl method. Chemiluminescence is accurate, reproducible, and appear to be well correlated with Kjeldahl assay technique. Without doubt, it is advantageous to the point of samples manipulation, that need no dangerous compounds, and by the way of her swiftness and her possible automation. Lastly, according with preliminary studies, this method seem as well practicable for solid samples as for liquid samples. This assay technique is therefore usefull in current practice to investigate nitrogen balance in every patient.
Feces↗
CD23 (Fc epsilon RII) activation induces the nitric oxide synthase pathway in human keratinocytes: possible relevance in cutaneous allergic diseases.
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Cells, Cultured↗
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↗
[Mastocytosis, classification, biological diagnosis and therapy].
In mast cell (MC) disorders (mastocytosis), clinical symptoms are caused by the release of chemical mediators from MCs, the pathologic infiltration of neoplastic MCs in tissues, or both. Cutaneous mastocytosis is a benign disease in which MC infiltration is confined to the skin. In pediatric cases cutaneous mastocytosis might regress spontaneously. Systemic mastocytosis (SM) is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow-derived myelomastocytic progenitors. The somatic c-kit mutation D816V is found in the majority of such patients. The natural clinical course in SM is variable. Whereas most patients remain at the indolent stage for many years, some have aggressive SM (ASM) at diagnosis. Other patients have an associated clonal hematologic none MC lineage disease (AHNMD). MC leukemia (MCL) is a rare disease variant characterized by circulating MCs and fatal disease progression. Two important diagnostic clues in SM are an increased serum tryptase level and the presence of abnormal mast cells in the bone marrow. The current review provides an overview of mastocytosis and its subvariants, the new classification of these diseases, a practical guide for the biological diagnosis and advances and future directions in therapy of these pathologies.
Bone Marrow Examination↗
[Therapeutic use of hematopoietic growth factors. I. Erythropoietin and thrombopoietin].
Modern molecular haematology is characterized by the great strides made in the use of cytokines, especially haematopoietic growth factors. These factors constitute a heterogeneous group of molecules that ensure the survival, proliferation and differentiation of the haematopoietic cells. Present detailed knowledge of the structure of the main haematopoietic growth factors and their receptors, and of the cloning and sequencing of their genes, permits the use of genetic engineering to produce recombinant human growth factors whose therapeutic applications have raised very great hopes for clinical haematology. Data obtained from several clinical studies have allowed the use of some of these molecules in France. This is the case concerning erythropoietin (Eprex, Recormon), G-CSF (Neupogen, Granocyte) and GM-CSF (Leucomax), each with specific uses. Others haematopoietic growth factors, such as stem cell factor (SCF) are presently evaluated for their clinical interest. Finally, interleukin 3 (IL3), whose in vitro activities seemed to be of potential interest, has been evaluated during clinical studies. Its toxicity and lack of specificity have been evidenced and do not allow its present utilization. The first part of this review is focused on the general structure and biological activity of haematopoietic growth factors and presents the actual therapeutic field of the use of erythropoietin and the promising application of recombinant thrombopoietin.
Anemia↗
[Therapeutic use of hematopoietic growth factors. II. GM-CSF and G-CSF].
The second part of this review on haematopoietic growth factors is focused on the therapeutic use of GM-CSF and G-CSF. Such therapeutic applications have raised very great hopes for clinical haematology. However, it should not be forgotten that these haematopoietic growth factors, which are very costly, are powerful two-edged weapons capable of triggering a cascade of reactions, and have a field of activity that often goes beyond the single highly specific property which it is hoped they possess. The risks and costs of their use are currently being evaluated. Waited developments concerning these molecules focus on three axes: a best use of factors already commercialized, especially concerning adaptation of posologies and new indications, the development of hybrid molecules from already known haematopoietic growth factors, possessing the advantages of respective factors, but not their disadvantages, the discovery of new haematopoietic growth factors with potential therapeutic application.
Animals↗