Interleukin 3 Promotes Histamine Synthesis in Hematopoietic Progenitors by Increasing Histidine Decarboxylase mRNA Expression

1993 ◽  
Vol 192 (1) ◽  
pp. 167-173 ◽  
Author(s):  
M. Dy ◽  
F. Machavoine ◽  
B. Lebel ◽  
A. Ichikawa ◽  
L.N. Gastinel ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Histidine Decarboxylase ◽  
Hematopoietic Progenitors ◽  
Interleukin 3 ◽  
Histamine Synthesis

scholarly journals Hematopoietic progenitors and interleukin-3-dependent cell lines synthesize histamine in response to calcium ionophore

Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3161-3169 ◽  
Author(s):  
M Dy ◽  
A Arnould ◽  
FM Lemoine ◽  
F Machavoine ◽  
H Ziltener ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Cell Lines ◽  
Histidine Decarboxylase ◽  
Calcium Ionophore ◽  
Ionophore A23187 ◽  
Hematopoietic Progenitors ◽  
Histamine Synthesis ◽  
Histamine Production ◽  
Dependent Cell

The calcium ionophore A23187 promotes histamine synthesis in murine bone marrow cells by increasing the expression of mRNA encoding histidine decarboxylase (HDC), the histamine-forming enzyme. The cells responsible for this biological activity copurify with hematopoietic progenitors in terms of density, light scatter characteristics, and rhodamine retention, similar to interleukin (IL) 3-induced histamine- producing cells. Yet, the effect of calcium ionophore is not mediated by IL-3. The most purified rhodamine-bright bone marrow subset contains 80% cells that respond to calcium ionophore by increased HDC mRNA expression. This high frequency makes the involvement of one particular progenitor subset in histamine synthesis unlikely. The finding that all IL-3-dependent cell lines tested so far exhibit increased histamine production and HDC mRNA expression in response to calcium influx lends further support to this notion. Cell lines requiring other growth factors or proliferating spontaneously lack this ability. Finally, it should be noted that IL-3-dependent cell lines do not produce histamine in response to their growth factor. It might, therefore, be suggested that the pathway transducing the signal for increased histamine synthesis after IL-3 receptor binding in normal hematopoietic progenitors is modified in these cell lines.

scholarly journals Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine hematopoietic progenitors

Blood ◽  
1994 ◽  
Vol 84 (4) ◽  
pp. 1098-1107
Author(s):  
F Salachas ◽  
E Schneider ◽  
FM Lemoine ◽  
B Lebel ◽  
M Daeron ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Histidine Decarboxylase ◽  
Bone Marrow Cells ◽  
Specific Inhibitor ◽  
Target Cells ◽  
Hematopoietic Progenitors ◽  
Interleukin 3 ◽  
Histamine Synthesis ◽  
Histamine Production ◽  
Marrow Cells

Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE.

scholarly journals Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine hematopoietic progenitors

Blood ◽  
1994 ◽  
Vol 84 (4) ◽  
pp. 1098-1107 ◽  
Author(s):  
F Salachas ◽  
E Schneider ◽  
FM Lemoine ◽  
B Lebel ◽  
M Daeron ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Histidine Decarboxylase ◽  
Bone Marrow Cells ◽  
Specific Inhibitor ◽  
Target Cells ◽  
Hematopoietic Progenitors ◽  
Interleukin 3 ◽  
Histamine Synthesis ◽  
Histamine Production ◽  
Marrow Cells

Abstract Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE.

scholarly journals Fibrinogen potentiates the effect of interleukin-3 on early human hematopoietic progenitors

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 800-806 ◽  
Author(s):  
YQ Zhou ◽  
JP Levesque ◽  
A Hatzfeld ◽  
AA Cardoso ◽  
ML Li ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Mitogenic Effect ◽  
Hematopoietic Progenitors ◽  
Human Fibrinogen ◽  
Rgd Peptides ◽  
Interleukin 3 ◽  
Fibrinogen Binding ◽  
Clonal Cultures ◽  
Beta 2 ◽  
Alpha V Beta 3

Abstract The effect of human fibrinogen on the proliferation of purified SBA- CD34+ human bone marrow progenitors was investigated in clonal cultures. Fibrinogen alone or in combination with erythropoietin had no significant effect. However, in the presence of recombinant human interleukin-3 (IL-3), fibrinogen increased significantly in a dose- dependent manner the number of mixed and burst-forming unit-ethrocyte-- derived colonies, whereas the number of other colonies did not significantly change. In the presence of fibrinogen, low concentrations of IL-3 (0.17 U/mL) produced three times more mixed colonies than without fibrinogen, reaching the number of colonies obtained with optimal concentrations of IL-3 (1.67 U/mL). Fibrinogen fragment D had the same effect in the presence of IL-3 as intact fibrinogen, whereas fibrinogen fragment E and human collagen IV did not. This effect was not mediated by integrins, because peptides or monoclonal antibodies that block fibrinogen binding on integrins alpha IIb beta 3, alpha v beta 3 (RGD-peptides), alpha m beta 2 (OKM-1), and alpha x beta 2 (HC1/1) did not affect the observed mitogenic effect. The mitogenic effect of fibrinogen and its D fragment was not mediated by induction of IL-6 or granulocyte--colony-stimulating factor secretion, because it was not inhibited by blocking antisera against these two growth factors. Our results indicate that fibrinogen potentiates the effect of IL-3 on primitive hematopoietic progenitors and suggest that the mitogenic effect of fibrinogen could be mediated via a specific mitogenic receptor that does not belong to the integrin family.

Autoregulation of histamine synthesis through H3 receptors in isolated fundic mucosal cells

1993 ◽  
Vol 265 (6) ◽  
pp. G1039-G1044 ◽  
Author(s):  
F. Hollande ◽  
J. P. Bali ◽  
R. Magous
Keyword(s):  
Gastric Mucosa ◽  
Endocrine Cells ◽  
Histidine Decarboxylase ◽  
Receptor Subtypes ◽  
Histamine Synthesis ◽  
H3 Receptors ◽  
Mucosal Cells ◽  
High Concentrations ◽  
The Relationship ◽  
Stimulation Of

Histamine plays an important role in the control of gastric acid secretion by activating H2 receptors located on parietal cells. In gastric mucosa, histamine is stored both in mast cells and in enterochromaffin-like cells, especially in rodents. It has been proposed that histamine may regulate its own synthesis and/or release through receptors pharmacologically distinct from H1- and H2-receptor subtypes. In this article, we studied the regulation by histamine of histidine decarboxylase (HDC) activity (enzyme responsible for the formation of histamine by decarboxylation of L-histidine) in a fraction of isolated rabbit gastric mucosal cells enriched in mucous and endocrine cells. Histamine and (R)-alpha-methylhistamine (H3 receptor agonist) dose dependently inhibited HDC activity with the same potency (mean effective concn: 32.2 +/- 0.7 and 50.5 +/- 3.1 pM, respectively) and efficacy (35 and 36% inhibition, respectively). In contrast, the H2 agonist dimaprit was devoid of effect. The H3 antagonist thioperamide was found to decrease the histamine- or (R)-alpha-methylhistamine-induced inhibition of HDC activity (mean ineffective concn = 28.3 +/- 1.8 and 9.87 +/- 0.8 nM, respectively), whereas H1 (promethazine) and H2 (ranitidine) antagonists were unable to affect HDC activity. Moreover, high concentrations of thioperamide (1-10 microns) increased histamine release from these cells. All these results allowed us to conclude that, in gastric mucosa, histamine downregulates its own synthesis (and perhaps release) through the stimulation of autoreceptors with pharmacological characteristics of H3 receptors. However, the relationship between histamine synthesis and release remains unclear and needs further investigation.

scholarly journals Cloning of rat interleukin-3 receptor beta-subunit from cultured microglia and its mRNA expression in vivo

1995 ◽  
Vol 15 (8) ◽  
pp. 5800-5809 ◽  
Author(s):  
K Appel ◽  
M Buttini ◽  
A Sauter ◽  
PJ Gebicke-Haerter
Keyword(s):  
Mrna Expression ◽  
Beta Subunit ◽  
Interleukin 3 ◽  
Receptor Beta

Implication of HIF-1α but Not HIF-2α in the Hypoxic Response of Human Hematopoietic Progenitors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4154-4154
Author(s):  
Yanyan Zhang ◽  
Adlen Foudi ◽  
Magali Berthebaud ◽  
Dorothee Buet ◽  
Peggy Jarrier ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Hematopoietic Cells ◽  
Receptor Expression ◽  
Metabolic Adaptation ◽  
Protein Accumulation ◽  
Mrna Levels ◽  
Hematopoietic Progenitors ◽  
Cd34 Cells ◽  
Cxcr4 Mrna

Abstract Maturing hematopoietic cells are exposed to hypoxia as they develop and migrate within the bone marrow microenvironment. Previous studies using non hematopoietic cell lines and monocytes showed that CXCR4 is strongly induced by hypoxia but little is known on the regulation of CXCR4 by hypoxia in the other hematopoietic cells and during hematopoietic development. We analyzed the expression and regulation of hypoxia-inducible transcription factor-1a (HIF1a) and 2a (HIF2a), the master regulators of metabolic adaptation to hypoxia, during hematopoiesis. Real time quantitative RT-PCR showed that HIF-1a mRNA was present on all the non hematopoietic and hematopoietic cells lines including HL-60, HEL, TF1, K562, KG1, U937, Jurkat and Mo7e. In contrast, HIF-2a mRNA expression was variable among the cell lines and was detected only at very low level in some cells such as KG1, Jurkat and HEL. Hypoxia exposure rapidly induced VEGF mRNA expression in the cells that expressed HIF-1a mRNA and exhibited HIF-1a protein accumulation. Interestingly, CXCR4 induction was observed only in the cells that exhibit significant expression of HIF-2a mRNA and HIF-2a protein accumulation. A strong correlation between HIF-2a mRNA levels and the induction of CXCR4 mRNA expression by hypoxia was found. Human CD34+ cells also expressed high levels of HIF-1a mRNA, whereas HIF-2a mRNA was barely detected. Interestingly, as observed for several myeloid cell lines, CD34+ cells exhibited a strong induction of VEGF expression in response to hypoxia and hypoxia mimetic agents cobalt chloride and desferrrioxamine whereas CXCR4 receptor expression was not induced suggesting that CXCR4 mRNA induction is related to the expression of HIF-2a. Altogether these data indicated that the hypoxic responses of human hematopoietic progenitors are independent of HIF-2a. Moreover, they establish that CXCR4 regulation by hypoxia is linked to HIF-2a protein expression.

Trib1 and Trib2 but Not Trib3 Degrade C/EBPá and Induce Acute Myelogenous Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2950-2950
Author(s):  
Priya Dedhia ◽  
Karen Keeshan ◽  
Maria Vega ◽  
Sacha Uljon ◽  
Lanwei Xu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mrna Expression ◽  
Acute Myelogenous Leukemia ◽  
Family Members ◽  
Myelogenous Leukemia ◽  
Hematopoietic Progenitors ◽  
E3 Ligases ◽  
Evolutionarily Conserved ◽  
Acute Myelogenous ◽  
Factor C

Abstract Trib1, Trib2, and Trib3 are mammalian homologues of the Tribbles protein family, an evolutionarily conserved group of proteins that can mediate proteasome-dependent degradation. Evidence suggests that these proteins function as adapters, where they recruit E3 ligases and enhance ubiquination of the target protein in order to promote its degradation. To date, increased Trib1 and Trib2 mRNA expression has been shown to correlate with acute myelogenous leukemia (AML) in humans and induces AML in mice; whereas Trib3 has not been associated with AML. In order to understand the effects of Trib family members in hematopoietic cells, we reconstituted mice with hematopoietic progenitors retrovirally expressing Trib1, Trib2, or Trib3. Trib1 and Trib2 mice developed AML whereas Trib3 mice did not. Our previous data suggested that Trib2-mediated degradation of the transcription factor, C/EBPα, is important for leukemogenesis. We now show that Trib1, like Trib2, strongly binds C/EBPα and induces its degradation. In contrast, Trib3 weakly binds C/EBPα and fails to induce its degradation. Consistent with the ability to strongly bind and degrade C/EBPα, Trib1 and Trib2, but not Trib3, block differentiation of myeloid cells. We are currently mapping the domains that account for the differences between Trib1/Trib2 and Trib3 in leukemogenesis. Together, our results strengthen the correlation between Trib-induced C/EBPα degradation and induction of AML. Furthermore, our data show that different Tribbles family members have distinct targets and understanding this specificity may provide opportunities to therapeutically target Tribbles.

scholarly journals Mast cells and their committed precursors are not required for interleukin-3-induced histamine synthesis in murine bone marrow: characteristics of histamine-producing cells

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1161-1169
Author(s):  
E Schneider ◽  
RE Ploemacher ◽  
B Nabarra ◽  
NH Brons ◽  
M Dy
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Marrow Cell ◽  
Cell Subset ◽  
Differentiation Potential ◽  
Murine Bone Marrow ◽  
Interleukin 3 ◽  
Biologic Activity ◽  
Histamine Synthesis ◽  
Murine Bone Marrow Cell

In the present study we investigate the nature of the murine bone marrow cell subset responsible for the marked increase in histamine synthesis induced by interleukin-3 (IL-3). Because mast cells, and eventually their committed precursors, represent a potential source of histamine in this context, we examined their possible participation in this biologic activity with particular attention. We provide evidence that neither of these populations respond to IL-3 in terms of histamine synthesis and that other differentiated end cells or stromal components of the bone marrow are also not involved in this phenomenon. Starting from these findings, we further characterized the immature hematopoietic compartment responsible for IL-3-induced histamine synthesis using fluorescence-activated cell sorter (FACS) sorting based on rhodamine retention or wheat germ agglutinin (WGA) affinity. These procedures have allowed us to ascribe the following features to histamine-producing cells: (1) They belong to a low-density, progenitor- enriched bone marrow subset containing cells of relatively important size and internal structure. (2) The highest histamine levels are generated by the rhodamine-bright fraction of this population, while the most primitive rhodamine-dull cells do not express this biologic activity. (3) Histamine-producing cells do not copurify with colony- forming units in spleen day 7 and day 12 in WGA-bright fractions. (4) Their enrichment is associated with increased frequencies of cells forming colonies in methylcellulose (CFU-C), suggesting the involvement of several progenitors with partially limited differentiation potential in this biologic activity.

Sign in / Sign up

Export Citation Format

Share Document