Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to lethally irradiated mice increased the rate of animal survival. Dose modification factor was 1.20 when 4.5 micrograms/mouse of rhG-CSF was given daily for 14 days after whole body irradiation. Haematological examinations revealed that rhG-CSF increased the number of blood-circulating leukocytes, neutrophils, monocytes and erythrocytes, but not that of lymphocytes and thrombocytes. Spleen weight and number of endogenous spleen colonies were also increased by rhG-CSF treatment compared with the values for mice irradiated only.
 ...
PMID:Effect of recombinant human granulocyte colony-stimulating factor on survival in lethally irradiated mice. 137 42

We have investigated the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on hemopoietic reconstitution after bone marrow transplantation (BMT) following lethal irradiation in mice. Mice received a daily administration of 10 micrograms/kg rG-CSF or control vehicle one through 21 days after BMT. Spleen colony-forming units (CFU-S), granulocyte-macrophage colony-forming units (CFU-GM), megakaryocyte colony-forming units (CFU-Meg), and erythroid burst-forming units (BFU-E) increased in both bone marrow and spleen of the rG-CSF-treated mice as compared with the control. This increase was evident during the administration period. In spite of the increase in the progenitor cells in bone marrow and spleen, only a recovery of neutrophils was accelerated in peripheral blood. Thus rG-CSF accelerated granulopoietic recovery in the BMT mice, with an enhanced recovery of the stem cells and the progenitors for erythrocytes and megakaryocytes. These results indicate the potential clinical usefulness of rG-CSF in the treatment of patients undergoing BMT.
 ...
PMID:Acceleration of the hemopoietic reconstitution in mice undergoing bone marrow transplantation by recombinant human granulocyte colony-stimulating factor. 171 Aug 41

Acute infection of Trypanosoma (T.) cruzi to C3H/HeN mice caused the induction of a higher level of serum colony stimulating factor (CSF) activity to support the proliferation of mouse bone marrow cells. The CSF activity reached a maximum 2 days after the infection and declined thereafter. Spleen cells of the T. cruzi-infected mice showed higher levels of responsiveness to CSF in L929-conditioned medium, mouse recombinant GM-CSF and infected mouse sera as compared with normal mouse spleen cells. The induction of CSF-responding cells became plateau 4 days after the infection and it decreased thereafter. In concomitant with the production of CSF activity in the infected mouse sera, large granular cells bearing high intensity of Mac-2 antigen increased in the infected mouse spleen. These cells were nylon nonadherent and displayed inhibitory effect on T cell response to Con A. These findings indicate that T. cruzi infection induces augmentation of in vivo CSF production, leading to the abnormal proliferation of CSF-responding cells and that augmented production of, and responsiveness to, CSF might be one of important mechanisms responsible for the induction of immune abnormalities in T. cruzi-infected mice.
 ...
PMID:Increase in colony stimulating factor (CSF) in serum and augmentation of CSF responsiveness of lymphoid mononuclear cells by acute Trypanosoma cruzi infection in mice. 210 2

Spleen cells from mice with chronic Trypanosoma cruzi infection generate a minimal plaque-forming response to SRBC in vitro. Addition of granulocyte-macrophage (GM)-CSF to cultures of spleen cells from chronically infected mice restored the plaque-forming cells (PFC) response to normal levels. Splenic adherent cells from chronically infected mice were deficient in their ability to reconstitute the PFC response of accessory cell-depleted normal spleen cells. Preincubation of splenic adherent cells from infected mice with GM-CSF restored their ability to reconstitute the PFC response of adherent cell depleted cultures. Ia Ag expression by splenic adherent cells from chronically infected mice was significantly lower compared to Ia Ag expression of cells from normal mice. Incubation of splenic adherent cells from chronically infected mice for 48 h with GM-CSF increased levels of Ia Ag expression to approximately those of uninfected mice. Peritoneal macrophages from infected mice produced IL-1 after incubation with GM-CSF at levels equivalent to those produced by similarly treated control macrophages. Spleen cells from chronically infected mice showed significant induction of IL-2 mRNA after GM-CSF treatment, and the addition of the anti-IL-2 mAb to GM-CSF supplemented cultures of spleen cells from infected mice blocked the restoration of the anti-SRBC PFC response. Thus, the ability of GM-CSF to restore the anti-PFC response to SRBC appears to involve the up-regulation of accessory cell function that includes increased Ia Ag expression and the induction of IL-1 production. These events also involve increased IL-2 production with resultant up-regulation of the response to SRBC by spleen cells from infected mice. Finally, it was shown that treatment of infected mice with rGM-CSF completely restored their depressed PFC production in vivo.
 ...
PMID:Recombinant granulocyte-macrophage colony-stimulating factor restores deficient immune responses in mice with chronic Trypanosoma cruzi infections. 211 33

Murine marrow cells infected with a retroviral vector (MPZen) bearing a granulocyte-colony-stimulating factor (G-CSF) cDNA insert were transplanted into lethally irradiated recipients to study the effects of autocrine production of G-CSF in normal hemopoietic cells. Most animals remained healthy with no evidence of tissue damage throughout the observation period (4-30 wk) despite high circulating G-CSF levels (range 2,000-26,000,000 U/ml). A dramatic neutrophilic granulocytosis was observed in all hemopoietic tissues with neutrophilic infiltration occurring in the lung and liver. Spleen, peritoneal, and peripheral blood cellularity increased approximately three-, two-, and eightfold, respectively, but total bone marrow cell counts remained unchanged. Progenitor cell numbers granulocyte-macrophage colony-forming cell (GM-CFC), granulocyte colony-forming cell (G-CFC), burst-forming unit-erythroid (BFU-E), colony-forming unit-erythroid (CFU-E) and mixed colony-forming cells (Mix-CFC) were elevated between 10-100-fold in the spleen, peritoneal cavity, and peripheral blood, but were unaffected or slightly depressed in the marrow. No tumors developed in syngeneic recipients transplanted with bone marrow or spleen cells from such mice, confirming the nonneoplastic nature of the hyperplasia induced by chronic G-CSF stimulation. These experiments also indicated the stable integration of MPZen vectors in infected cells, as evident from the continuous expression of the inserted gene for at least 6 mo, and from the ability of infected stem cells from the primary recipients to express the gene in lethally irradiated secondary recipients.
 ...
PMID:Long-term exposure to retrovirally expressed granulocyte-colony-stimulating factor induces a nonneoplastic granulocytic and progenitor cell hyperplasia without tissue damage in mice. 247 88

In order to investigate the role of the human spleen on hematopoiesis, hematopoietic stem cells and stimulates were evaluated in fetal and adult spleens. BFU-E and CFU-C were existed in 20 weeks and 23 weeks fetal spleens (BFU-E 145 +/- 45/10(5) mononuclear cells, CFU-C 55 +/- 6/10(5) mononuclear cells). In adult spleen, a few stem cells were recognized, which may be contaminated from peripheral blood in sinus of the spleen. We tested conditioned media from adult spleen cells for the stimulative activity on the in vitro growth of BFU-E and CFU-C from bone marrow mononuclear cells. Spleen conditioned medium stimulated proliferation of these precursor cells. It seemed that PHA-stimulated spleen conditioned medium augmented BFU-E, whereas CFU-C growth was suppressed. Adult and fetal spleens were studied immunohistochemically using anti-G-CSF, GM- CSF and erythropoietin antibodies. The cells with G-CSF and GM-CSF were shown in fetal spleens. In adult spleens, however, only GM-CSF was detected.
 ...
PMID:[Spleen and hematopoiesis]. 260 Oct 40

Previous efforts from our laboratory have investigated the mechanisms responsible for dimethylnitrosamine (DMN)-induced suppression of T cell responses. These studies suggested that such changes in T cell activity were most likely to be due to alterations in the down-regulatory signals controlling T cell activation. Accordingly, the production of PGE2, a potent inhibitor of T cell activation, was examined in macrophages obtained from animals exposed to either DMN or vehicle in vivo. The production of PGE2 was determined in macrophages representing various stages of activation (responsive, primed and fully activated) and various stages of differentiation (CSF-1-derived or GM-CSF-derived macrophages). All peritoneal macrophages obtained from DMN-exposed animals demonstrated enhanced production of PGE2 following stimulation with either endotoxin or IFN-gamma as compared to macrophages obtained from vehicle-exposed macrophages. Moreover, the enhanced levels of PGE2 were due to increased PGE2 production rather than to shifts in the kinetics of PGE2 production and utilization. CSF-1- and GM-CSF-induced bone-marrow-derived macrophages (BMDM) produced minimal levels of PGE2, regardless of the in vitro stimulation of cells obtained from either vehicle or DMN treatment groups. Spleen cells obtained from DMN-exposed animals produced significantly higher amounts of PGE2 following endotoxin stimulation compared to control splenocytes. Splenocytes from DMN-exposed animals also demonstrated a suppressed proliferative response to the mitogen Con A. However, when splenocytes from DMN-exposed animals were co-cultured with indomethacin they demonstrated Con A-stimulated proliferative responses similar to the responses of vehicle control splenocytes. These results demonstrate that DMN exposure results in increased PGE2 production by macrophages and that this increase in PGE2 production may be responsible for suppressed T cell responses observed in DMN-exposed animals.
 ...
PMID:Augmented macrophage PGE2 production following exposure to dimethylnitrosamine in vivo: relevance to suppressed T cell responses. 280 73

Radiation-induced L8313 leukemia bearing mice (L8313 mice) had marked granulocytosis with splenomegaly. Hemopoietic stem cells and progenitors increased in the spleen but not in the bone marrow. Spleen conditioned-medium and serum from L8313 mice induced the formation of granulocyte-macrophage colonies (CFU-GM), erythroid bursts (BFU-E) and mixed colonies (CFU-Mix). Bone marrow conditioned medium did not show such activity. A cell line (STIL-3) was established from the spleen cells of L8313 mice. Surface marker analysis showed that the established cells were suppressor T cell. The cells produced IL-3 and GM-CSF in vitro, and induce essentially the same "leukemic" response in recipient mice. Inoculation of STIL-3 in diffusion chamber also induced leukemoid reaction, i.e. a marked granulocytosis with splenomegaly. Therefore, L8313 leukemia may be linked to an abnormality of growth and production of hemopoietic factors in hemopoietic regulatory cells.
 ...
PMID:Physiopathological studies on granulocyte-macrophage colony stimulating factor and multi colony stimulating factor producing leukemia, L8313, induced by irradiation of C3H mice. 287 75

Spleen mononuclear cells of C3H/HeN mice were cultivated with mitomycin C-treated tumor cells, X5563, MH134, MM48, MM46, and FM3A/R, all of which were of syngeneic origin, in a medium containing normal syngeneic mouse serum but not FCS. There was a proliferative response to X5563, MH134, and MM48, but not to the two other tumor cells, MM46 and FM3A/R. The responder spleen cells were found to be nonadherent cells with a phenotype of Thy-1-L3T4-Lyt2-Ig-Macl-, which were neither mature T and B cells nor mature macrophage/granulocytes. It was also found that the proliferation of these nonadherent no-marker cells was mediated by tumor cell-derived soluble factors but not by direct stimulation with tumor cells. The responsible factor was a molecule(s) with a Mr of 23 to 25 kDa, which had a CSF activity inducing granulocyte (G)-, macrophage (M)- and G + M-colonies in the bone marrow cells. Neutralization tests of this factor-induced proliferation of spleen cells revealed that a major part of the factor may be GM-CSF or a molecule closely related to it. Incubation of spleen mononuclear cells with these GM-CSF-like tumor cell factors resulted in induction of myeloblastic/promyelocytic cells with a phenotype of Mac-1+2+Ia+ Thy-1-L3T4-Lyt2-Ig- in the spleen cell cultures, which could suppress mitogenic responses of the spleen cells to T and B cell mitogens. GM-CSF-like activity could also be detected in the serum of mice bearing X5563, MH134, and MM48, but not in those bearing MM46 and FM3A/R. Subcutaneous inoculation of C3H/HeN mice with these X5563, MH134, and MM48 tumor cells generated massive metastasis in the lung and lymph nodes, whereas MM46 and FM3A/R produced no macroscopic tumor cell metastasis. These results strongly suggest the possibility that in some tumor cell-host systems, a GM-CSF-like factor(s) produced constitutively by the tumor cells may play an important role in the development of tumor metastasis, mediating through suppression of lymphoid tissues of the host.
 ...
PMID:Production of colony-stimulating factor by tumor cells and the factor-mediated induction of suppressor cells. 296 7

In order to clarify the mechanism(s) of increased splenic hematopoiesis noted in lipopolysaccharide (LPS)-injected mice, the effects of spleen cell-conditioned medium (SPCM) on megakaryocyte colony (CFU-meg) formation and early erythroid (BFU-e) differentiation were investigated. After spleen cells from LPS-injected mice were incubated for 3 days, the SPCM was assayed for megakaryocyte colony-stimulating factor (Meg-CSF) in CFU-meg assay and for burst-promoting activity (BPA) and erythropoietin (Epo) in erythroid colony assays (i.e., CFU-e, BFU-e). Colony formation of CFU-meg and BFU-e peaked with the addition of 30 and 10-15% SPCM, respectively. Spleen cells from LPS-injected mice produced Meg-CSF and BPA when compared with controls. However, conditioned medium from spleen cells depleted of phagocytic cells had low Meg-CSF and BPA. SPCM did not contain detectable quantities of Epo. It appears likely that local splenic production of Meg-CSF and BPA may affect proliferation of CFU-meg and erythroid progenitor cells in the spleen.
 ...
PMID:Megakaryocyte colony-stimulating factor and burst-promoting activity in LPS-treated mouse spleen cell-conditioned medium. 326 23


1 2 3 4 Next >>