Search PubMed⌕ Search

Biomedical subjects

Y Denizot

Publications and source records attributed to Y Denizot.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of lipoxygenase metabolites of arachidonic acid on the growth of human mononuclear marrow cells and marrow stromal cell cultures.

The effects of various lipoxygenase metabolites of arachidonic acid (AA) were investigated on the growth of freshly isolated human bone marrow mononuclear cells and marrow stromal cell cultures. LTB4, LXA4, LXB4, 12-HETE and 15-HETE (1 microM) decreased [3H]-thymidine incorporation on marrow stromal cell cultures without affecting cell number. Only 12-HETE showed a dose-response effect on [3H]-thymidine incorporation. While LTB4 (1 microM) decreased thymidine incorporation on marrow mononuclear cells, LTC4, LXA4, LXB4, 12-HETE and 15-HETE had no effect. The lipoxygenase inhibitor NDGA had no effect on both cell types suggesting no role of endogenous lipoxygenase metabolites on cell growth. These results suggest no important role of lipoxygenase metabolites of AA on the proliferation of human marrow mononuclear cells and marrow stromal cell cultures.

Arachidonic Acid↗
PubMed1997

Production, metabolism and effect of platelet-activating factor on the growth of the human K562 erythroid cell line.

The human immature K562 erythroid cell line was studied for its capacity to produce and to metabolize the phospholipid molecule platelet-activating factor (PAF). K562 cells produced PAF under calcium ionophore stimulation. Lyso PAF and acetyl-CoA (the acetate donor molecule for the acetylation of lyso PAF into PAF) had no effect on the amounts of PAF produced by ionophore-stimulated cells. The metabolism of PAF and lyso PAF by K562 cells was compared to that of freshly-isolated human bone marrow erythroblasts and blood erythrocytes. K562 cells rapidly metabolized [3H]PAF and [3H]lyso PAF with 1-alkyl analogue of phosphatidylcholine as the major metabolic product. In contrast, blood erythrocytes did not. PAF acetylhydrolase activity levels in K562 cells and bone marrow erythroblasts were similar and higher than in blood erythrocytes. PAF (1-100 nM) stimulated [3H]thymidine incorporation in K562 cells grown in low serum concentration, a non-metabolizable PAF agonist being more potent than PAF to stimulate thymidine incorporation. PAF receptor mRNA was detected in K562 cells by polymerase chain reaction on reverse transcripts. The present study demonstrates that K562 cells produce and metabolize PAF and underlines the putative role of erythroid precursors in the modulation of bone marrow PAF concentrations. The effect of PAF on the growth of K562 cells might be mediated through PAF receptors suggesting a potential role of PAF on the proliferation and functions of human erythroid marrow precursors.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Spontaneous and inducible production of leukaemia inhibitory factor by human bone marrow stromal cells.

Leukaemia inhibitory factor (LIF) acts on the growth and differentiation of haematopoietic cells. By using a specific enzyme-linked immunosorbent assay for human LIF, we demonstrate that human bone marrow stromal cells produce LIF. LIF synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMAS). LIF production in response to PMA is PKC-dependent since the two PKC inhibitors sphingosine and staurosporine markedly diminished it. Interleukin 1alpha (IL-1alpha), IL-1beta, IL-3, IL-6, IL-8, tumour necrosis factor (TNF-alpha) and SCF (both at 10 ng/ml) stimulate LIF production. By contrast macrophage colony-stimulating factor (M-CSF), granulocyte (G)-CSF, GM-CSF, basic fibroblast growth factor (bFGF), platelet-activating factor (PAF), protaglandin E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4 (LTC4) did not. These results suggest that bone marrow stromal cells might represent a major source for the cytokine-regulated local production of LIF inside human bone marrow.

Bone Marrow Cells↗
PubMed1997

Production and metabolism of platelet-activating factor by human bone marrow cells.

Platelet-activating factor (PAF) is a phospholipid mediator of inflammation present in the human bone marrow. Freshly isolated human mononuclear bone marrow cells and marrow stromal cell cultures produced PAF under calcium ionophore (2 microM) and LPS (10 micrograms/ml) stimulation. By contrast, M-CSF (1000 U/ml), GM-CSF (100 ng/ml), IL1, IL3, IL6 and stem cell factor (10 ng/ml) did not stimulate PAF production. Marrow stromal cells produced 50-fold more PAF than freshly isolated mononuclear marrow cells, suggesting that stromal cells might be the major source of the human marrow-derived PAF. Mononuclear marrow cells and stromal cell cultures metabolized PAF with 1-alkyl-2-acyl-glycerophosphocholine as the major metabolic product. PMSF and p-BPB decreased the catabolism of PAF by freshly isolated marrow cells, but not by stromal cell cultures. While stromal cells rather than haematopoietic progenitors might be a major source of the human bone-marrow-derived PAF, both cell types metabolize it, suggesting their putative role in the regulation of PAF concentration in the human bone marrow.

Bone Marrow↗
PubMed1997

Presence and metabolism of lyso platelet-activating factor in human bone marrow.

Lyso platelet-activating factor (PAF) is the precursor of PAF, an inflammatory phospholipid molecule present in human bone marrow. The present study shows that in healthy volunteers lyso PAF concentrations are significantly lower (P = 0.0001, Mann-Whitney U-test) in bone marrow plasma (594 +/- 67 ng/ml, n = 47) than in blood plasma (1448 +/- 99 ng/ml, n = 31). Marrow plasma lyso PAF concentrations are similar in patients with lymphoid and nonlymphoid malignancies as compared with controls. Freshly isolated mononuclear marrow cells and cultures of marrow stromal cells contain lyso PAF. Experiments with [3H]lyso PAF indicate that human mononuclear bone marrow cells and marrow stromal cells actively acylate lyso PAF into a 1-alkyl analogue of phosphatidylcholine. Results of this investigation indicate: (1) that lyso PAF is present in human marrow cells and plasma; and (2) that marrow cells and stromal cells metabolize it, thus suggesting their role in the regulation of lyso PAF amounts in human bone marrow.

Aged↗
PubMed1997

Effects of lipidic mediators on the growth of human myeloid and erythroid marrow progenitors.

Freshly isolated human marrow mononuclear cells produce lipidic compounds such as PAF and leukotrienes. These lipidic molecules act on human marrow myelopoiesis and erythropoiesis by modulating the growth of committed progenitors (CFU-GM and BFU-E) in vitro. Nanomolar concentrations of leukotriene B4 and C4 stimulate the growth of human marrow CFU-GM. In contrast, micromolar concentrations of lipoxygenase inhibitors (NDGA and BW755C) decrease their growth suggesting a role for endogenous lipoxygenase metabolites in this process. Micromolar concentrations of prostaglandin E2 up-regulate and down-regulate the growth of marrow BFU-E and CFU-GM, respectively. In contrast, the other cyclooxygenase metabolites have no effect. Recent studies indicate that nanomolar concentrations of PAF decrease the growth of CFU-GM and BFU-E from purified marrow CD34+ cells. Together these results indicate that lipidic mediators act on human myelopoiesis and erythropoiesis. However at this time the mechanisms and molecular signals mediating the effects of lipidic molecules on human marrow cells are unexplored.

Bone Marrow↗
PubMed1997

Platelet-activating factor and antagonists modulate DNA synthesis in human bone marrow stromal cell cultures.

Platelet-activating factor (PAF) is present in the human bone marrow. We have investigated the effect of PAF and antagonists (BN 52,021 and CV 3988) on the growth of human marrow stromal cells. PAF (1 microM) stimulates and PAF antagonists (0.1-1 microM) inhibit [3H]thymidine incorporation in cells grown in 5% serum. The catabolism of PAF by stromal cells was inhibited by CV 3988 suggesting the presence of specific PAF receptor on cells. PAF and antagonists (0.1 nM-10 microM) had no effect on cells cultured in high serum concentration (20%) or in low serum concentration (1%) with 0.5 ng/ml of basic fibroblast growth factor (bFGF). This study indicates for the first time that PAF modulates the serum-induced but not the bFGF-induced growth of marrow stromal cells. The interactions between PAF and stromal cells during inflammatory marrow events such as myelofibrosis deserve to be assessed.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Cytokine and lipid mediator blood concentrations after coronary artery surgery.

UNLABELLED: This study investigates whether increased levels of cytokines and lipid mediators may be associated with complications after coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC). Hemodynamic measurements and blood samples were obtained in 32 patients before and after the end of ECC and at the 6th and the 24th postoperative hours. Coagulation and pulmonary and cardiovascular functions were specifically assessed postoperatively at the same time. Patients with cardiovascular dysfunction had higher interleukin 8 (IL-8) levels. Higher platelet-activating factor (PAF) and decreased PAF acetylhydrolase activity (AHA, the enzyme that inactivates PAF) levels were found in patients with moderate cardiovascular dysfunction. Interleukin 6 (IL-6), IL-8, and AHA levels correlated with most hemodynamic parameters and creatine phosphokinase myocardial band levels obtained after surgery. Patients with severe lung injury had lower PAF, 6-keto prostaglandin (Pg)F1alpha, and PgE2 levels and higher thromboxane (Tx) B2 concentrations compared with patients without lung injury. Increased IL6 levels were only associated with moderate lung injury. Impaired hemostasis was associated with higher IL6 levels. AHA, IL-6, and IL-8 seem to be associated with cardiovascular dysfunction. The IL-6 blood levels and the ratio of TxB2/6 keto-PgF1alpha blood levels are increased during post-CABG lung injury. These results identify an association between specific post-CABG complications and the systemic inflammatory response. The clinical significance of this association remains to be evaluated. IMPLICATIONS: Patients with pulmonary, cardiovascular, or hemostasis dysfunction after cardiopulmonary bypass demonstrate aberrancies in a variety of cytokines and lipid mediators in arterial blood or plasma. The relationship between these findings and inflammatory response-induced complications remains to be determined.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Leukemia inhibitory factor concentrations in the bone marrow plasma of healthy subjects and patients with hematologic malignancies.

Several cytokines may play a role in the pathogenesis of various hematopoietic malignancies. As cytokines work locally, we have investigated leukemia inhibitory factor (LIF) concentrations in the bone marrow plasma of healthy subjects and patients with hematopoietic malignancies by using a specific enzyme-linked immunosorbent assay. LIF levels in patient's samples were significantly higher in bone marrow plasmas (330.3 +/- 43.6 pg/ml; n = 29) than LIF levels in blood plasmas (178.9 +/- 16.8 pg/ml; n = 43) (p = 0.0006, Mann-Whitney U-test). Marrow stromal cells which constitutively produce LIF and enhance their synthesis in response to LPS and PMA might be the cell source of the bone marrow-derived LIF. No statistical difference was documented between marrow plasma LIF concentrations of 24 patients with hematological malignancies and healthy controls. At the present time, the role of LIF in the human marrow cytokine network requires further evaluation.

Bone Marrow↗
PubMed1997

Spontaneous and inducible production of macrophage colony-stimulating factor by human bone marrow stromal cells.

Macrophage Colony-Stimulating Factor (M-CSF), which is permanently present in blood and human bone marrow, regulates the proliferation, differentiation and functions of cells of the mononuclear-phagocytic lineage. By using Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) we demonstrate that human marrow stromal cells express two types of M-CSF transcripts that are translated into the secreted form and the membrane anchored form. By using a specific and sensitive ELISA, we found that the spontaneous production of M-CSF by human marrow stromal cells is enhanced after stimulation with lipopolysaccharide (LPS), phorbol myristic acetate (PMA) and most interestingly by the lipidic mediator of inflammation platelet-activating factor (PAF). Thus, marrow stromal cells might represent a regulated cell source of bone marrow-derived M-CSF. These results not only emphasize the importance of the bone marrow environment in the control of human hematopoiesis but also evidence, for the first time, the potential role of PAF in the marrow cytokine network during inflammatory processes.

Bone Marrow↗
PubMed1996

PAF and haematopoiesis XII: macrophage colony-stimulating factor (M-CSF) decreases platelet-activating factor (PAF) acetylhydrolase production in macrophagic J774 cells.

Platelet-activating factor (PAF) is a phospholipid mediator with major immunoregulatory activities. Macrophages produce PAF acetylhydrolase activity, which regulates blood PAF concentrations. Macrophage colony-stimulating factor (M-CSF) is involved in the differentiation and functions of cells from the monocytic/macrophagic lineage. We found that murine macrophagic J774 cells metabolized PAF with lyso PAF as the major metabolite product. As in mouse plasma, the metabolism of PAF by J774 cells was not inhibited by PMSF, p-BPB, DTNB and quinacrine, M-CSF (100-5000 U/ml) significantly decreased PAF acetylhydrolase activity of the J774 cell without exhibiting a significant effect on cell growth. Elevated concentrations of M-CSF are found in blood and tissues during inflammatory states. It could be suggested that a decreased PAF catabolism by tissue macrophages in response to M-CSF may induce local elevated PAF concentrations, thus amplifying the inflammatory response.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

PAF and haematopoiesis. X. Macrophage colony-stimulating factor and granulocyte macrophage colony-stimulating factor enhance platelet-activating factor acetylhydrolase production by human blood-derived macrophages.

Platelet-activating factor (PAF), a phospholipid autacoid with potent regulatory functions, is synthesized by stimulated monocytes. Macrophages are a source of the plasma acetylhydrolase activity (AHA) which regulates PAF concentrations. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are involved in the differentiation and functions of cells from the monocytic/macrophagic lineage. This work reports that M-CSF and GM-CSF stimulated AHA production by human blood monocyte-derived macrophages in a time- and dose-dependent manner. After 7 days of culture without serum, a 6- and 4-fold increase was found in cells treated with M-CSF (1000 U/ml) and GM-CSF (50 ng/ml), respectively. M-CSF (up to 1000 U/ml) and GM-CSF (up to 10 ng/ml) did not induce PAF production by human blood monocytes. While GM-CSF (10 ng/ml) and interleukin-1 (10 U/ml) stimulated M-CSF production from monocyte-derived macrophages, PAF did not. These results indicate that M-CSF and GM-CSF enhance AHA production by human blood-derived macrophages cultured in low serum concentrations. Clearly the effects of growth factors on AHA production in vivo deserve to be assessed.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗