scholarly journals Immunologic stimulation of early murine hematopoiesis and its abrogation by cyclosporin A

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 851-856 ◽  
Author(s):  
SA Burstein ◽  
SK Erb ◽  
JW Adamson ◽  
LA Harker
Keyword(s):  
Immune Response ◽  
Cyclosporin A ◽  
Progenitor Cells ◽  
Pokeweed Mitogen ◽  
Normal Rabbit Serum ◽  
Lymphocyte Function ◽  
Spleen Cells ◽  
Stimulation Of

Abstract Mice injected chronically with antiplatelet serum develop an increase in the number of megakaryocytic progenitor cells compared to animals given normal rabbit serum. To examine the specificity of this response, progenitor cells giving rise to megakaryocyte, granulocyte-macrophage, erythroid, and mixed-cell colonies were assayed after injection of various heterosera or saline. All four colony types increased in the serum-treated groups. Since the in vitro proliferation of hematopoietic progenitor cells is promoted by supernatants of mitogen-stimulated spleen cells, we hypothesized that the immune response following antiserum administration resulted in the in vivo activation of T lymphocytes which produced or led to the production of colony stimulating activities. To test this hypothesis, cyclosporin A, a preferential inhibitor of T lymphocyte function, was given to mice concurrently with antiserum and also added to spleen cell cultures in the presence of pokeweed mitogen. Cyclosporin A abrogated the antiserum- related increases in progenitor cell numbers in vivo and the production of colony stimulating activity in vitro. The results suggest that the immune response related to antiserum administration results in the in vivo production of hematopoietic colony stimulating activities that may be identical to those produced in vitro by mitogen-stimulation of spleen cells.

scholarly journals Immunologic stimulation of early murine hematopoiesis and its abrogation by cyclosporin A

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 851-856 ◽  
Author(s):  
SA Burstein ◽  
SK Erb ◽  
JW Adamson ◽  
LA Harker
Keyword(s):  
Immune Response ◽  
Cyclosporin A ◽  
Progenitor Cells ◽  
Pokeweed Mitogen ◽  
Normal Rabbit Serum ◽  
Lymphocyte Function ◽  
Spleen Cells ◽  
Stimulation Of

Mice injected chronically with antiplatelet serum develop an increase in the number of megakaryocytic progenitor cells compared to animals given normal rabbit serum. To examine the specificity of this response, progenitor cells giving rise to megakaryocyte, granulocyte-macrophage, erythroid, and mixed-cell colonies were assayed after injection of various heterosera or saline. All four colony types increased in the serum-treated groups. Since the in vitro proliferation of hematopoietic progenitor cells is promoted by supernatants of mitogen-stimulated spleen cells, we hypothesized that the immune response following antiserum administration resulted in the in vivo activation of T lymphocytes which produced or led to the production of colony stimulating activities. To test this hypothesis, cyclosporin A, a preferential inhibitor of T lymphocyte function, was given to mice concurrently with antiserum and also added to spleen cell cultures in the presence of pokeweed mitogen. Cyclosporin A abrogated the antiserum- related increases in progenitor cell numbers in vivo and the production of colony stimulating activity in vitro. The results suggest that the immune response related to antiserum administration results in the in vivo production of hematopoietic colony stimulating activities that may be identical to those produced in vitro by mitogen-stimulation of spleen cells.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (3) ◽  
pp. 648-659 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Stuart Schlossman ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Suppressor Cells ◽  
Specific Response ◽  
Spleen Cells ◽  
X Irradiation

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

scholarly journals Lithium enhancement of megakaryocytopoiesis in culture: mediation via accessory marrow cells

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 172-176 ◽  
Author(s):  
C Chatelain ◽  
SA Burstein ◽  
LA Harker
Keyword(s):  
T Lymphocyte ◽  
Conditioned Media ◽  
Pokeweed Mitogen ◽  
Accessory Cell ◽  
Lymphocyte Function ◽  
Spleen Cells ◽  
Hematopoietic Progenitors ◽  
Marrow Cultures ◽  
Marrow Cells

Abstract To examine the effect of lithium (Li) on early megakaryocytopoiesis, murine marrow megakaryocytic (CFU-M) and granulocyte-macrophage (CFU-C) progenitors were assayed in vitro with and without addition of lithium chloride (LiCl) to culture. At 2 mM LiCl, the numbers of CFU-M- and CFU- C-derived colonies were increased to 146% +/- 8% and 128% +/- 6% of controls, respectively (p less than 0.005). Enumeration of megakaryocytes per colony showed a 78% increase of colonies (p less than 0.05) containing from 6 to 22 cells, suggesting an increased proliferative capacity of CFU-M in the presence of LiCl. Conditioned media from spleen cells cultured in the presence of both pokeweed mitogen (PWM-SCM) and 2 mM Li increased the numbers of CFU-M and CFU-C to 157% +/- 8% and 183% +/- 8%, respectively (p less than 0.025), compared to control cultures stimulated by PWM-SCM alone. Since the production of active colony-stimulating activities (CSA) from mitogen- stimulated conditioned media requires T lymphocytes, we hypothesized that the enhancement of the growth of early hematopoietic progenitors in marrow cultures was due to a Li-induced CSA production by accessory marrow cells, rather than a direct effect of Li on stem cells. To test this, cyclosporin-A (CyA), a T-lymphocyte function inhibitor known to suppress CSA production in PWM-SCM, was added to marrow cultures in the presence of 2 mM Li. CyA (3 micrograms/ml) abrogated the Li-induced enhancement of CFU-M and CFU-C growth, but had no effect on colony formation when added alone. The data suggest that the Li-induced enhancement of early megakaryocytopoiesis and granulocytopoiesis is due to local production of CSA(s) by an accessory cell population and requires the integrity of T-lymphocyte function.

scholarly journals DELETION OF HAPTEN-BINDING CELLS BY A HIGHLY RADIOACTIVE 125I CONJUGATE

1972 ◽  
Vol 136 (2) ◽  
pp. 305-317 ◽  
Author(s):  
Dov Theo Golan ◽  
Yves Borel
Keyword(s):  
Immune Response ◽  
Normal Mouse ◽  
Mouse Spleen ◽  
Spleen Cells ◽  
Protein Carrier

Exposure of normal mouse spleen cells in vitro to highly 125I-labeled dinitrophenyl (DNP)-protein carrier conjugates specifically inactivated cells able to mount an immune response to that hapten after in vivo challenge. The deletion was hapten specific and independent of the radioactive carrier to which the hapten was bound. DNP-binding cells were inactivated by radioactivity that was not part of the hapten, but was solely confined to the carrier moiety. The deletion of the anti-DNP response lasted 2–3 wk and could be specifically inhibited.

scholarly journals THE EFFECTS OF ANTIGENS AND OF PHYTOHEMAGGLUTININ ON RABBIT SPLEEN CELL SUSPENSIONS

1966 ◽  
Vol 124 (4) ◽  
pp. 621-634 ◽  
Author(s):  
G. Harris ◽  
R. J. Littleton
Keyword(s):  
Dna Synthesis ◽  
Spleen Cell ◽  
Cell Suspensions ◽  
Red Cells ◽  
Specific Response ◽  
Spleen Cells ◽  
Sheep Red Cells ◽  
Stimulation Of

Phytohemagglutinin (PHA) stimulated the rate of DNA synthesis in rabbit spleen cell suspensions. Unlike antigens, previous immunization to PHA was not necessary and the specific response could not be transferred by macrophages, although lymphocytes primed by incubation in PHA were able to stimulate other spleen cells not directly exposed to PHA. When rabbits were stimulated by in vivo immunization with antigens, spleen cells proliferating in response to antigen were stimulated to divide by in vitro contact with PHA. Using the technique of specific hemolytic plaque formation by individual cells synthesizing γM-antibody to sheep red cells (plaque-forming cells), no evidence was obtained that stimulation of cell division by PHA resulted in specific antibody formation, although the presence of antigen resulted both in stimulation of cell proliferation and the production of plaque-forming cells. The presence of both sheep red cells and PHA in the medium of the same cell suspensions did not enhance the production of plaque-forming cells although there was a summative effect on DNA synthesis.

Abstract 894: Leptin Potentiates the Angiogenic Properties of Endothelial Progenitor Cells In Vitro and In Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nana-Maria Heida ◽  
Marco R Schroeter ◽  
I-Fen Cheng ◽  
Elena I Deryugina ◽  
Thomas Korff ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Tube Length ◽  
Endothelial Progenitor ◽  
Signal Transduction Inhibitors ◽  
Stimulation Of

Endothelial progenitor cells (EPC) have been reported to contribute to neovascularization. We have previously shown that the adipocytokine leptin may enhance the adhesive properties of EPC by upregulating specific integrins. To investigate whether the angiogenic effects of leptin may be mediated by modulation of EPC function, mononuclear cells were isolated from healthy human volunteers and cultivated under endothelial cell conditions for 7 days. In the matrigel assay, pretreatment of EPC with recombinant leptin for 24 hours dose-dependently enhanced their incorporation into tubular structures provided by mature endothelial cells. For example, 138.3 ± 7.6% (P = 0.001) and 145.3 ± 5.5% (P = 0.0001) CM-DiI-labeled EPC were detected after stimulation with 10 and 100 ng/mL leptin, respectively (control-treated EPC defined as 100%). Furthermore, in the spheroid angiogenesis assay, stimulation of EPC with 10 ng/mL leptin increased the number of sprouts (P < 0.0001) and tube length (P < 0.0001) of coincubated mature endothelial cells, and the outgrowth of EPC (P < 0.0001). Addition of 100-fold excess of leptin-neutralizing or leptin-receptor-binding antibodies completely reversed these effects. Moreover, EPC adhesion onto endothelial cell tubules could be reduced by addition of RGD peptides (from 159 ± 13.7% to 101.8 ± 14.6%; P = 0.02), or of neutralizing antibodies against αvβ3 (from 165.3 ± 11.8% to 103.8 ± 13.3%; P = 0.006) or αvβ5 (to 93.5 ± 15.8%; P = 0.005). Further experiments using specific signal transduction inhibitors (10 μM of LY294002, PD98059, or SB203580), as well as Western blot analysis, revealed that leptin signaling in EPC involves phosphoinositide-3 kinase and p42/44, but not by p38 MAP kinase. The effects of leptin could also be confirmed under in vivo conditions. Stimulation of EPC with 100 ng/mL leptin potentiated the insprout of newly formed avian vessels into collagen onplants placed on the chorion allantoic membrane of chicken embryos (angiogenic index, 0.58 ± 0.24) compared to control-treated EPC (0.44 ± 0.27; P = 0.07) and endothelial basal medium alone (0.31 ± 0.26; P = 0.0007). Thus, our in vitro and in vivo results suggest that the angiogenic effects of leptin may partly depend on its specific interaction with endothelial progenitor cells.

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