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)

The radioprotective properties of flk2/flt3 ligand (FL) were evaluated in lethally irradiated mice. Optimum survival rates (70-80%) were observed when 5 to 20 microg of FL was administered at both 20 and 2 hours before LD100/30 radiation. Administration of FL well in advance of irradiation was essential for conferring most of the radioprotection, since a single dose given at -20 hours still resulted in a significant survival rate (65%), whereas a single dose given at -2 hours was relatively nonprotective. Histopathologic examination at 7 and 9 days postirradiation revealed significant myelopoietic activity in the bone marrow (BM) of FL-treated mice, suggesting that their survival might be due to sparing of radiosensitive hematopoietic cells. By comparison, the BM of mice treated with phosphate-buffered saline was extremely hypocellular and remained that way until they died of bacterial infection. Hematopoietic assays confirmed a marked stimulation of early white blood cell (WBC) recovery in the BM and blood of FL-protected mice relative to PBS-treated controls. By day 21, FL-protected mice showed circulating WBC numbers that were higher than preirradiation values; however, their BM colony-forming units in culture were still depressed. Moreover, these mice experienced a prolonged anemia and thrombocytopenia. These findings are discussed in light of the restricted subset of hematopoietic progenitors shown to be responsive to FL in vitro.
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PMID:Radioprotective effects of flk2/flt3 ligand. 962 Feb 85

We have developed a murine model that facilitates the structural and functional analysis in vivo of dendritic cell (DC)-mediated phagocytosis of prostate epithelial cells. Recombinant human Flt3 ligand (rhFL) expands the number of dendritic cells in lymphoid and non-lymphoid tissues of mice. We show that rhFL also induced the ingress of dendritic cells into murine prostate, which involutes via epithelial apoptosis after surgical castration. Intact or castrated C57BL/6 and syngeneic transgenic adenocarcinoma of mouse prostate (TRAMP) mice were treated with rhFL or PBS control. Prostate and spleen were then studied by flow cytometry and immunohistochemistry. The number of prostatic CD11c+ and CD11b+ dendritic cells increased significantly in rhFL-treated mice compared with PBS-treated control mice and this effect was greatly augmented by castration of the mice. The immunophenotype of rhFL-mobilized prostatic cells was consistent with that of Langerhans cells (MHC class II+, CD11c+,CD11b+, DEC-205+, CD8 alpha-).MHC class II+ and CD11c+ dendritic cells that were present in the prostate glands of rhFL-treated and castrated C57BL/6 mice were intimately associated with TUNEL+ inclusions, which suggests that Langerhans-type dendritic cells in prostate participated in the clearance of apoptotic cells. Expression of MHC class II, CD54, CD80 and CD86 by prostatic dendritic cells was not up-regulated after castration and freshly isolated rhFL-induced prostate cells were unable to prime allogeneicT cells unless they were activated by culture either on plastic or with recombinant soluble CD40 ligand. Our data suggest that rhFL-mobilized prostatic dendritic cells resemble the functionally immature dendritic cells, which reside in peripheral tissues and contribute to the maintenance of peripheral tolerance.
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PMID:Flt3 ligand expands dendritic cell numbers in normal and malignant murine prostate. 1212 Dec 27

Flt3 ligand (Flt3-L) is a growth factor for dendritic cells and induces type 1 T cell responses. We recently reported that Flt3-L prevented OVA-induced allergic airway inflammation and suppressed late allergic response and airway hyper-responsiveness (AHR). In the present study we examined whether Flt3-L reversed allergic airway inflammation in an established model of asthma. BALB/c mice were sensitized and challenged with OVA, and AHR to methacholine was established. Then mice with AHR were randomized and treated with PBS or 6 microg of Flt3-L i.p. for 10 days. Pulmonary functions and AHR to methacholine were examined after rechallenge with OVA. Treatment with Flt3-L of presensitized mice significantly suppressed (p < 0.001) the late allergic response, AHR, bronchoalveolar lavage fluid total cellularity, absolute eosinophil counts, and inflammation in the lung tissue. There was a significant decrease in proinflammatory cytokines (TNF-alpha, IL-4, and IL-5) in bronchoalveolar lavage fluid, with a significant increase in serum IL-12 and a decrease in serum IL-5 levels. There was no significant effect of Flt3-L treatment on serum IL-4 and serum total IgE levels. Sensitization with OVA significantly increased CD11b(+)CD11c(+) cells in the lung, and this phenomenon was not significantly affected by Flt3-L treatment. These data suggest that Flt3-L can reverse allergic airway inflammation and associated changes in pulmonary functions in murine asthma model.
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PMID:Flt-3 ligand reverses late allergic response and airway hyper-responsiveness in a mouse model of allergic inflammation. 1506 83

Dendritic cells (DCs) are unique antigen presenting cells that are immature prior to their encounter with an antigen. Exposure to allergens induces the maturation of DCs with changes in morphology and presence of dendrites. Here, we demonstrate that the DCs in the lungs of ovalbumin (OVA)-sensitized and challenged mice are more mature owing to their pronounced dendrites than the DCs in the lungs and spleen of PBS-treated mice, which are immature and possess cytoplasmic veils. Intermediate to these two groups are the DCs in the Flt3 ligand-treated group that exhibit comparatively fewer dendrites and cytoplasmic veils and hence are classified as semimature. Presence of large numbers of well-developed mitochondria and rough endoplasmic reticulum in myeloid DCs from both lungs and spleen of OVA-sensitized and challenged mice indicate greater functional activity. Additionally, DCs from the OVA-sensitized and challenged mice also exhibit fat and glycogen stores, which are indicative of a mature population. In addition, treatment of the animals with Flt3 ligand attenuated airway hyperresponsiveness to methacholine in OVA-sensitized and challenged mice. These data suggest that morphological features could be indicative of the maturation and distinct functional state of DCs, and this could be associated with underlying mechanisms of Flt3 ligand-induced immunomodulation in allergic asthma.
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PMID:Flt3 ligand generates morphologically distinct semimature dendritic cells in ovalbumin-sensitized mice. 1718 33

Cell-mediated immune (CMI) responses are crucial in the protection against tuberculosis. 6-kDa early secretary antigenic target (ESAT-6) is an important T-cell antigen recognized by protective T cells in animal models of infection with Mycobacterium tuberculosis. Flt3 ligand (FL) is a growth factor of dendritic cell (DC), which, as a powerful antigen presenting cell (APC), is essential for CMI response. In this study, we constructed a recombinant DNA vaccine encoding ESAT-6 and FL. The recombinants were identified by restriction enzyme digestion and sequence analysis. Subsequently, the recombinants were transfected into glomerular mesangial cells (GMCs) of rat. The expressed proteins were detected by Western blot. C57BL/6 female mice were immunized three times with the recombinant plasmids. The results showed that immunization with pIRES-ESAT-6 plasmid induced an obvious T-cell response compared with controls (mice immunized with PBS, pIRES or BCG). However, mice immunized with pIRES-ESAT-6-FL presented a more stronger T helper 1 (Th1)-biased response, accompanied by higher levels of lymphocytes proliferation, elevated production of Th1 cytokines (IFN-gamma and IL-2) by spleen cells, as well as increased specific antibody in sera, together with lower levels of Th2 cytokines (IL-4 and IL-10). Our results suggested that EAST-6 was a useful vaccine candidate and FL might be a powerful adjuvant, which could effectively promote T cell-mediated immune response.
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PMID:Recombinant DNA vaccine of the early secreted antigen ESAT-6 by Mycobacterium tuberculosis and Flt3 ligand enhanced the cell-mediated immunity in mice. 1859 29

The biology of plasmacytoid dendritic cells (pDCs) in tumors is an emerging area of investigation. pDCs populate many human solid tumors, including lung cancer. The aim of our study was to understand the role of pDCs in pulmonary metastases during the treatment with conventional antitumor agents. For this purpose, C57Bl/6 mice were inoculated with the metastatic cell line B16-F10 or B16-Flt3L cells. The administration of doxorubicin significantly reduced the amount of pulmonary metastases in both experimental models. It is interesting to note that, 5 hours after injection, doxorubicin-induced tumor cell death was associated with higher influx of pDCs to the lung, which at 24 hours populated the mediastinal lymph nodes. In this context, lung tumor-derived pDCs obtained from mice treated with doxorubicin had higher levels of MHC I and MHC II that well correlated with the higher proliferation rate of CD4 and CD8 T cells, compared with PBS mice. Siglec-H and PD-L1 levels were not altered on lung tumor-associated pDCs derived from doxorubicin-treated and PBS-treated mice. In addition, lung tumor-associated pDCs obtained from mice treated with doxorubicin released higher levels of granzyme B. The administration of 2 consecutive doses of doxorubicin in lung tumor-bearing mice showed that B16-Flt3L-implanted mice had lower tumor burden than B16-F10-implanted mice. In conclusion, our data highlight the crucial role of the proinflammatory pDCs for the adaptive antitumor immunity. Strategies aiming at modulating pDC phenotype and activity in the tumor site might prove to be novel and effective, enhancing the conventional/actual antitumor strategies.
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PMID:Plasmacytoid dendritic cells contribute to doxorubicin-induced tumor arrest in a mouse model of pulmonary metastasis. 2471 55