Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue factor activity was detected in human mononuclear cells cultured with E. coli endotoxin in vitro. The effecient concentration of endotoxin inducing significant tissue factor development was in excess of 10(-3) microgram/ml, and a dose response type relationship was seen between them. The activity developed after culturing for 2 hr and increased up to 6 hr, and thereafter no significant increase was observed. Although the activity was detected both in cell extract and on cell surface, the main activity seemed to exist on the cell surface. No correlation was observed between the synthetic rate of nucleic acid and the rate of development of the activity. Although the activity was detected also in a granulocyte preparation, it was significantly less than that in mononuclear cells. The development of activity was observed when lymphocytes were cultured in RPMI 1640 medium, MEM, and in autologous serum. However, the activity was not observed when cultured in Hanks solution and PBS, in which the main difference from RPMI was the absence of amino acids, and in autologous serum containing sodium citrate which was added for elimination of Ca++ from serum. Moreover, actinomycin D suppressed the development of activity, and the same was noted at low culture temperature. These results suggest that some metabolic change of the cell membrane triggered by endotoxin may induce the development of tissue factor in cells.
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PMID:Development of tissue factor activity in mononuclear cells cultured in vitro. 35 95

Despite the emergence of newer antibiotic treatments, group B streptococcal infection still carries a high mortality rate in the newborn and is characterized by reduced neutrophil proliferative pools, neutrophil storage pools, neutropenia, and polymorphonuclear cell dysfunction. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) has recently been demonstrated to induce neutrophilia and modulate neutrophil proliferative pools and neutrophil storage pools in the newborn rat. We therefore investigated the adjuvant effect of rhG-CSF given to group B streptococcus (GBS) septic Sprague-Dawley newborn (less than 36 h) rats treated with and without antibiotic therapy. After inoculation of GBS, a GBS survival curve established the LD50 at 50 h to be approximately 3 X 10(6) organisms/gm. Newborn rats were divided into four treatment groups after GBS inoculation. rhG-CSF was administered at the same time as GBS inoculation. At 24 h, there was approximately 100% survival in all groups. However, by 72 h after GBS inoculation, there was a significant difference in survival. Group 1, PBS/Alb, had a survival rate of 4%; group 2, rhG-CSF, 9%; group 3, antibiotics, 28%; and group 4, antibiotics plus rhG-CSF, 91% (p less than or equal to 0.001). Additionally, when rhG-CSF was administered prophylactically (6 h before GBS), a similar significant synergistic effect in survival was demonstrated with granulocyte colony stimulating factor plus antibiotics versus antibiotics alone (70 versus 10%) (p less than or equal to 0.01). These preliminary data suggest that either simultaneous or prophylactic pulse administration of rhG-CSF may have a synergistic and protective effect on survival in antibiotic-treated experimental GBS in the neonatal rat.
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PMID:Prophylactic or simultaneous administration of recombinant human granulocyte colony stimulating factor in the treatment of group B streptococcal sepsis in neonatal rats. 169 23

During states of increased demand, neonatal host defense is characterized by dysregulation of granulopoiesis, resulting in a high incidence of neutropenia. This study investigated the modulation of neonatal rat hematopoiesis by 14-d administration of recombinant human (rh) IL-6, rh-granulocyte-colony stimulating factor (G-CSF), or sequential combination of rhIL-6 and rhG-CSF. Specifically, newborn Sprague-Dawley rats were treated with either rhIL-6 (5 micrograms/kg/d for 14 d), rhG-CSF (5 micrograms/kg/d for 14 d), rhIL-6 for 7 d followed by rhG-CSF for 7 d, PBS/BSA for 7 d followed by rhG-CSF for 7 d, or PBS/BSA for 14 d. RhIL-6 alone significantly increased the peripheral platelet count during the latter part of the 2nd wk of administration (d 13: 980 +/- 42 versus 716 +/- 23 x 10(3)/mm3) (p = less than 0.001) (mean +/- SEM). Treatment with rhIL-6 for 7 d followed by rhG-CSF significantly increased the peripheral neutrophil count compared with 7 d of PBS/BSA and 7 d of G-CSF (d 14 absolute neutrophil count 4888 +/- 12 versus 2720 +/- 317/mm3) (p = less than 0.05). Similarly, sequential rhIL-6/rhG-CSF significantly increased the d-14 bone marrow neutrophil storage pool (9873 +/- 882 versus 3564 +/- 159/mm3) (p = less than 0.005). Lastly, sequential rhIL-6/rhG-CSF induced the highest increase in bone marrow (p less than 0.01) and liver/spleen CFU-GM pool (p less than 0.001) compared with any other treatment group. These studies suggest that rhIL-6 alone is associated with a significant increase in the neonatal platelet count.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequential administration of interleukin-6 and granulocyte-colony stimulating factor in newborn rats: modulation of newborn granulopoiesis and thrombopoiesis. 172 8

Single-pulse administration of either recombinant human granulocyte-monocyte colony stimulating factor or recombinant human granulocyte colony stimulating factor to newborn rats has previously been demonstrated to increase the peripheral neutrophil count and modulate bone marrow (BM) neutrophil pools. In our present study, we investigated the effects of 7 d of either recombinant murine granulocyte-monocyte colony stimulating factor (rmGM-CSF) (75 micrograms/kg/d) or recombinant murine IL-3 (rm IL-3) (10 micrograms/kg/d) on newborn rat myelopoiesis. Sprague Dawley newborn rats (greater than or equal to 24 h) were injected (intraperitoneally) daily for 7 d with either rmGM-CSF, rmIL-3, or PBS/BSA. rmGM-CSF induced a significant increase in the peripheral neutrophil count on d 3 (p less than 0.03) and d 7 (p less than 0.001) (75% increase). Additionally, rmGM-CSF induced a 50% increase in the BM neutrophil storage pool (p less than 0.025). rmIL-3 increased the BM colony forming unit-granulocyte monocyte pool (p less than 0.001); however, it failed to increase the peripheral neutrophil count or BM neutrophil storage pool. Neither CSF increased the BM neutrophil proliferative pool or BM colony forming unit-granulocyte monocyte proliferative rate. Additionally, 7 d of rmGM-CSF with or without antibiotics did not synergistically alter the mortality rate after group B streptococcol inoculation. This study suggests that rmIL-3 appears to stimulate more neonatal myeloid committed progenitor cell activity compared with rmGM-CSF. Optimal modulation of neonatal myelopoiesis may require the use of a sequential combination of hematopoietic CSF, namely an early-acting CSF followed by a more lineage myeloid-specific CSF.
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PMID:Modulation of neonatal myelopoiesis in newborn rats after 7 days' administration of either granulocyte-monocyte colony stimulating factor or interleukin-3. 189 56

Infections by gram-negative bacteria are one of the major causes of death in newborns. Bacterial clearance is deficient in septic neonates, which seems to increase their susceptibility to infections. In this study, we observed a significant improvement in clearance of Klebsiella pneumoniae in newborn wistar rats inoculated by intraperitoneal via with 800 mg k soybean phosphatidylcholine (PC), compared to the control group injected with PBS (p 0.05). The overall survival rate was improved (p 0.05) and the white blood cell counts showed a greater leukocytosis and neutrophilia during the peak of bacteremia in the PC treated animals. Circulating levels of interleukin-6 were greater in the PC group, which developed an intense splenic hematopoiesis of the granulocyte (p 0.05) and megakariocyte series (p 0.01). No significant changes were observed in bone marrow granulocyte deposits in both study groups. The improvement in survival rate, the changes in leukocyte counts and the splenic hematopoiesis may be associated with the increased production of IL-6. These results suggest that IL-6 plays a role in the protection mechanism induced by PC in this experimental model of newborn septicemia. PC seems to be an immunomodulator of the acute response to gram-negative bacterial infection.
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PMID:[Phosphatidylcholine induces an increase in the production of interleukin-6 and improves survival of rats with neonatal sepsis caused by Klebsiella pneumoniae]. 749 35

Interleukin-6 (IL-6) is a pleiotropic cytokine that enhances the maturation of megakaryocytes. In mice, in vivo treatment with IL-6 results in elevated platelet counts both in untreated animals and after myelosuppressive therapy. In this study, we assessed the effect of continuous infusion of IL-6 in sublethally irradiated (7 Gy) mice on peripheral blood cell counts and progenitor cells in bone marrow and spleen. Female Swiss mice were treated by continuous infusion with 1 or 10 micrograms IL-6 per day for 7 or 14 days. Continuous infusion of IL-6 for 7 days resulted in elevated levels of circulating IL-6 (mean: 1872 pg/mL vs. 100 pg/mL for phosphate-buffered saline [PBS]-treated controls) and in an accelerated reconstitution of platelets starting at day 12 after irradiation. In IL-6-treated animals, the 50% pretreatment platelet count was reached on day 15 vs. day 21 for irradiated controls receiving no IL-6. Treatment with IL-6 for 14 days resulted in a further increase in platelet counts, exceeding the pretreatment counts. The number of colony-forming units-megakaryocyte (CFU-Mk) was significantly elevated from day 6 to 18 in the spleen but not in bone marrow. To assess the contribution of extramedullary megakaryocytopoiesis in the spleen to IL-6-induced platelet recovery, IL-6 was also administered to splenectomized mice. The stimulatory effect of IL-6 on platelet recovery was preserved in these animals, indicating that megakaryocytopoiesis in the spleen did not contribute to the accelerated recovery of platelets. The neutrophil counts were elevated during IL-6 treatment and became similar to controls after cessation of therapy, whereas the numbers of colony-forming units-granulocyte/macrophage (CFU-GM) in the bone marrow were elevated from day 9 to 24 in all animals treated with 10 micrograms IL-6 per day. In conclusion, continuous infusion of IL-6 stimulates platelet recovery after irradiation without increasing the number of CFU-Mk and conversely stimulates the proliferation of myeloid progenitor cells without an effect on neutrophil reconstitution.
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PMID:Continuous infusion of interleukin-6 in sublethally irradiated mice accelerates platelet reconstitution and the recovery of myeloid but not of megakaryocytic progenitor cells in bone marrow. 824 64

Polysaccharides (EP) isolated from large scale plant cell cultures of Echinacea purpurea, have been shown to activate human and murine phagocytes. In this study we investigated the influence of EP on the nonspecific immunity in immunodeficient mice. EP was effective in activating peritoneal macrophages isolated from animals after administration of cyclophosphamide (CP) or cyclosporin A (CsA). EP-treated macrophages exhibited increased production of tumor necrosis factor-alpha (TNF) and enhanced cytotoxicity against tumor target WEHI 164 as well as against the intracellular parasite Leishmania enrietti. After a CP-mediated reduction of leukocytes in the peripheral blood, the polysaccharides induced an earlier influx of neutrophil granulocytes as compared to PBS-treated controls. EP treatment of mice, immunosuppressed with CP or CsA, restored their resistance against lethal infections with the predominantly macrophage-dependent pathogen Listeria monocytogenes and predominantly granulocyte-dependent Candida albicans. Further, the effects of EP in allogeneic bone marrow chimeric mice are discussed. These findings may have therapeutical implications in prophylactic treatment of opportunistic infections.
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PMID:Polysaccharides isolated from plant cell cultures of Echinacea purpurea enhance the resistance of immunosuppressed mice against systemic infections with Candida albicans and Listeria monocytogenes. 837 43

We report that acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), which removes progenitor cells from cell cycle, in combination with granulocyte-colony stimulating factor (G-CSF) can significantly improve myelorestoration following irradiation (7 Gy). Peripheral blood, spleen and bone marrow (BM) cell recovery and progenitor cell reconstitution [IL-3-responsive colony-forming cells (CFC) and high proliferative potential colony-forming cells (HPP-CFC)] were studied. Studies on the optimal schedule of AcSDKP administration revealed maximal effects on progenitor cells when AcSDKP was administered as a continuous infusion for 3 d starting 24 h prior to irradiation and used in combination with G-CSF. The numbers of CFC and HPP-CFC in the BM were significantly increased following irradiation in mice receiving AcSDKP and G-CSF as compared to either drug alone. The numbers of CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on days 10 and 14 as compared to AcSDKP alone, but not G-CSF. Similarly, CFC and HPP-CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on day 18 as compared to mice receiving PBS and G-CSF. These studies suggest that AcSDKP in combination with G-CSF may have potential for the protection of progenitor cells in patients undergoing intensive chemo- and/or radiotherapy.
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PMID:In vivo haemoprotective activity of tetrapeptide AcSDKP combined with granulocyte-colony stimulating factor following sublethal irradiation. 882 83

As it is not known what changes to leucocyte homeostasis are mandatory for effective adjuvant action, the biological relevance of systemic changes elicited by different vaccine formulations can only be interpreted in the context of the immunological outcomes. We used flow cytometry to quantify the changes in leucocyte subsets induced in mice intradermally immunized with SAMA4 (adjuvant group), outer membrane proteins (OMP) purified from Actinobacillus pleuropneumoniae (OMP antigen group), SAMA4 adjuvanted OMP (OMP vaccine group), or phosphate-buffered saline (PBS: control group). This approach allowed direct comparisons to be made between the effects of antigen, adjuvant or antigen-adjuvant complexes on immune effector cell populations. Antigens complexed with the liposome-iscom hybrid adjuvant, SAMA4, generated strong antibody responses and cytotoxic T-cell activity in animals immunized intradermally, reflecting remobilization and recruitment of specific cell populations. Splenomegaly, due to granulocytosis, monocytosis and megakaryocytosis, was most prominent in the OMP vaccine group. Histological examination of spleen sections confirmed that these changes were due primarily to splenic haematopoiesis. Circulating numbers of granulocytes and monocytes increased significantly (P < 0.05) in the blood of the OMP vaccine group, as did granulocyte numbers in the lungs (P < 0.05). No changes in T- and B-cell numbers were detected by flow cytometry in the spleens, lungs or blood over the 28-day period in any treatment group. Thymocyte numbers (predominantly CD4+CD8+ cells) in the OMP vaccine group fell by 95% within 3 days of immunization. Identical cellular responses were obtained when an innocuous antigen, ovalbumin, was complexed with SAMA4 instead of OMP, thus demonstrating that the adjuvant effects of SAMA4 were due to synergistic interaction between antigen and adjuvant and not due to the presence of toxic components. The association of strong adaptive immune responses with such complex changes in leucocyte homeostasis induced by complexing adjuvant and antigen suggested that the changes were important for effective vaccination and were not purely circumstantial.
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PMID:Flow cytometric analysis of cellular changes in mice after intradermal inoculation with a liposome-iscom adjuvanted vaccine. 951 63

Peripheral blood stem cell (PBSC) support in breast cancer patients allows high-dose chemotherapy, but tumor cell contamination of the PBSCs is a potential source of relapse. Specific carcinoma cell killing can be obtained by retargeting activated T cells with bispecific antibody BIS-1, directed against epithelial glycoprotein-2 and CD3. To purge epithelial tumor cells from the PBSCs of breast cancer patients, activation of T cells in PBSCs and T-cell retargeting by BIS-1 was studied. PBSCs, obtained by leukapheresis after chemotherapy and recombinant human granulocyte colony-stimulating factor, were cultured in the presence of PBS, interleukin-2, OKT3, or interleukin-2/OKT3 for induction of T-cell activation. Subsequently, lysis of epithelial tumor cell lines by activated T cells of PBSCs in the presence or absence of BIS-1 was assessed with the 51Cr-release assay or immunocytochemical staining. The effect on PBSC hematopoietic colony formation (HCF) was evaluated by the granulocyte macrophage colony-stimulating units assay. Prior to activation, PBSCs from breast cancer patients contained higher levels of CD8+ T cells than peripheral blood from healthy volunteers (P < 0.05). The potential of PBSCs to sustain tumor cell lysis was increased after all prior activations and was further enhanced by BIS-1. Maximal BIS-1 effect was observed after OKT3 activation of PBSCs for 72 h (P < 0.0005), inducing a >3 log depletion of tumor cells. HCF was not affected by prior OKT3 activation and/or BIS-1. In conclusion, specific tumor cell lysis by PBSCs can be obtained in vitro by OKT3 activation and BIS-1 retargeting of T cells, without affecting HCF. At present, studies are evaluating this format for future clinical application.
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PMID:Purging of epithelial tumor cells from peripheral blood stem cells by means of the bispecific antibody BIS-1. 1087 8


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