Reticuloendothelial System

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Bart De Geest - One of the best experts on this subject based on the ideXlab platform.

Fons A J Van De Loo - One of the best experts on this subject based on the ideXlab platform.

  • a crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the Reticuloendothelial System in mediating experimental arthritis
    Arthritis Research & Therapy, 2010
    Co-Authors: O J Arntz, Jeroen Geurts, Sharon Veenbergen, Miranda B Bennink, Ben T Van Den Brand, Shahla Abdollahiroodsaz, Wim B Van Den Berg, Fons A J Van De Loo
    Abstract:

    Introduction: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Biologics directed against tumor-necrosis-factor (TNF)-α are efficacious in the treatment of RA. However, the role of TNF receptor-1 (TNFR1) in mediating the TNFα effects in RA has not been elucidated and conflicting data exist in experimental arthritis models. The objective is to investigate the role of TNFR1 in the synovial lining cells (SLC) and the Reticuloendothelial System (RES) during experimental arthritis. Methods: Third generation of adenovirus serotype 5 were either injected locally in the knee joint cavity or Systemically by intravenous injection into the retro-orbital venous sinus to specifically target SLC and RES, respectively. Transduction of organs was detected by immunohistochemistry of the eGFP transgene. An adenoviral vector containing a short hairpin (sh) RNA directed against TNFR1 (HpTNFR1) was constructed and functionally evaluated in vitro using a nuclear factor-kappaB (NF-κB) reporter assay and in vivo in streptococcal cell wall-induced arthritis (SCW) and collagen-induced arthritis (CIA). Adenoviruses were administered before onset of CIA, and the effect of TNFR1 targeting on the clinical development of arthritis, histology, quantitative polymerase chain reaction (qPCR), cytokine analyses and T-cell assays was evaluated. Results: Systemic delivery of Ad5.CMV-eGFP predominantly transduced the RES in liver and spleen. Local delivery transduced the synovium and not the RES in liver, spleen and draining lymph nodes. In vitro, HpTNFR1 reduced the TNFR1 mRNA expression by three-fold resulting in a 70% reduction of TNFα-induced NF-κB activation. Local treatment with HpTNFR1 markedly reduced mRNA and protein levels of interleukin (IL)-1β and IL-6 in SLC during SCW arthritis and ameliorated CIA. Systemic targeting of TNFR1 in RES of liver and spleen by Systemic delivery of Ad5 virus encoding for a small hairpin RNA against TNFR1 markedly ameliorated CIA and simultaneously reduced the mRNA expression of IL-1β, IL-6 and Saa1 (75%), in the liver and that of Th1/2/17-specific transcription factors T-bet, GATA-3 and RORγT in the spleen. Flow cytometry confirmed that HpTNFR1 reduced the numbers of interferon (IFN)γ (Th1)-, IL-4 (Th2)- and IL-17 (Th17)-producing cells in spleen. Conclusions: TNFR1-mediated signaling in both synovial lining cells and the Reticuloendothelial System independently played a major pro-inflammatory and immunoregulatory role in the development of experimental arthritis.

Kyunghan Lee - One of the best experts on this subject based on the ideXlab platform.

  • hydrazinonicotinamide prolongs quantum dot circulation and reduces Reticuloendothelial System clearance by suppressing opsonization and phagocyte engulfment
    Nanotechnology, 2012
    Co-Authors: Kyungho Jung, Jin Won Park, Jinyoung Paik, Eun Jeong Lee, Yearn Seong Choe, Kyunghan Lee
    Abstract:

    In this study, we investigated the effects of hydrazinonicotinamide (HYNIC)-a bifunctional crosslinker widely used to (99m)Tc radiolabel protein and nanoparticles for imaging studies-on quantum dot opsonization, macrophage engulfment and in vivo kinetics. In streptavidin-coated quantum dots (SA-QDots), conjugation with HYNIC increased the net negative charge without affecting the zeta potential. Confocal microscopy and fluorescence-activated cell sorting showed HYNIC attachment to suppress SA-QDot engulfment by macrophages. Furthermore, HYNIC conjugation suppressed surface opsonization by serum protein including IgG. When intravenously injected into mice, HYNIC conjugation significantly prolonged the circulation of SA-QDots and reduced their hepatosplenic uptake. Diminished Reticuloendothelial System clearance of SA-QDots and aminoPEG-QDots by HYNIC conjugation was also demonstrated by in vivo and ex vivo optical imaging. The effects of HYNIC on the opsonization, phagocytosis and in vivo kinetics of quantum dots were reversed by removal of the hydrazine component from HYNIC. Thus, surface functionalization with HYNIC can improve the in vivo kinetics of quantum dots by reducing phagocytosis via suppression of surface opsonization.

Christine E. M. Demore - One of the best experts on this subject based on the ideXlab platform.

  • Tumor Contrast Imaging with Gas Vesicles by Circumventing the Reticuloendothelial System
    Ultrasound in medicine & biology, 2019
    Co-Authors: Judy Yan, Melissa Yin, F. Stuart Foster, Christine E. M. Demore
    Abstract:

    Gas vesicles (GVs) are nanosized structures (45-800 nm) and have been reported to produce non-linear contrast signals, making them an attractive agent for molecular targeting of tumors. One barrier to their use for pre-clinical oncology studies is rapid uptake into the Reticuloendothelial System (RES) and consequent rapid decrease in contrast signal after infusion ends and low signal on reperfusion after a bubble burst sequence. The purpose of this study was to examine suppression of the RES and surface modification of GVs to prolong contrast circulation in tumors for ultrasound imaging. Ultrasound imaging to measure dynamics of contrast signal intensity in tumor models was carried out using a 21-MHz high-frequency array transducer with the Vevo 2100 ultrasound System. The non-linear contrast signal from intravenously injected GVs compared with peak enhancement was measured during contrast wash-out and on reperfusion after a contrast burst sequence. Disrupting the RES by saturating the macrophage population or chemically inhibiting the Kupffer cell population with gadolinium or Intralipid preserves 62%-88% of GVs' contrast enhancement relative to peak during the wash-out phase and 32%-56% on reperfusion compared with 38% and 14%, respectively, for no disruption of the RES, indicating longer circulation of GVs in the tumor. Additionally, coating the GVs with 2-, 5- or 10-kDa polyethylene glycol (PEG) chains resulted in >70% contrast signal retention in the tumors during wash-out and, for 5- or 10-kDa PEG chains, a return to >45% of peak contrast signal on reperfusion. These findings indicate that GVs can be used as a contrast agent for tumor imaging and that disruption of the RES improved recirculation and maintained contrast enhancement caused by GVs in the tumors.

Michal Zimecki - One of the best experts on this subject based on the ideXlab platform.

  • alterations of tumor necrosis factor alpha and interleukin 6 production and activity of the Reticuloendothelial System in experimental obstructive jaundice in rats
    Hpb, 2002
    Co-Authors: Janusz Dawiskiba, Pawel Kornafel, Danuta Kwiatkowska, Michal Zimecki
    Abstract:

    Background Immunological changes are well recognised in obstructive jaundice. The aim of this study was to monitor plasma tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels in rats with obstructive jaundice. Methods The ability of splenocytes and peritoneal exudate cells (PEC) to produce these cytokines both spontaneously and on induction with lipopolysaccharide (LPS), was compared in rats with and without obstructive jaundice (OJ). The activity of the Reticuloendothelial System (RES) was also measured. Results Serum cytokine levels in OJ rats were higher than in control rats. PEC cultures produced significantly more IL-6, compared with control rats, declining thereafter. TNF-α activity in the splenocyte cultures of OJ rats was also higher than in the control group. Pronounced differences were found in the ability to produce TNF-α by PEC, i.e., TNF-α production was much stronger on day 7 in OJ rats than in controls. On day 14 TNF-α production was much lower and the spontaneous response was equal to the LPS-induced one. On day 21 the cells of OJ rats partially regained the ability to produce TNF-α RES activity of OJ rats was significantly suppressed in the liver and spleen, whereas the phagocytic activity in the lungs was elevated. Conclusion We have demonstrated that the immune reactivity of OJ rats, intially elevated, underwent subsequent depression. The study also revealed a major effect of the operation alone on the studied parameters.