clodronate liposomes monocyte depletion

Macrophages in the liver and spleen can be depleted within 24 h after a single i.v. clodronate-liposomes were assessed in human peripheral blood monocytes, as well as in polymorphonuclear leukocytes (PMNs), T cells, endothelial cells, and fibroblasts, both at rest and following activation. C57BL/6 mice require a higher dose of cisplatin to induce renal fibrosis and CCL2 correlates with cisplatin-induced kidney injury. Epub 2020 Aug 24. Clodronate was a gift of Roche Diagnostics (Mannheim, Germany). ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Macrophage/monocyte depletion by clodronate, but not diphtheria toxin, improves renal ischemia/reperfusion injury in mice. Clophosome ® with the clodronate molecules encapsulated in neutral liposomes is capable of achieving macrophage depletion of 80-90% in spleen after a single intravenous or intraperitoneal administration. Liposomes. Gel electrophoresis of nuclear extracts and … The purpose of this study was to develop a method for the depletion of macrophages from the peritoneal cavity and the omentum of the rat. WT or Cx3cr1 GFP/+ mice were depleted of circulating monocytes using clodronate as previously described . 19 However, when delivered into phagocytic cells using liposomes as vehicles, clodronate accumulates in the cell and induces apoptosis after exceeding a threshold concentration. Littermate control or HUPO mice with established arthritis were administered clodronate-loaded liposomes (Liposoma B.V.) by retro-orbital injection at 200 μl or an equal volume of PBS. Although either system effectively depleted circulating monocytes and resident mononuclear phagocytes, depletion was most marked in diphtheria toxin–treated mice. This pharmacological treatment has been demonstrated to induce specific apoptotic death in monocytes and phagocytic macrophages. The phagocyte immediately recognizes the liposomes as foreign particles and proceeds with destroying these invading particles. Mice were injected with 10 μL/g of clodronate liposomes i.v. Clophosome ® - Clodronate Liposomes (Neutral). The only proven effective method for specifically targeting clodronate to phagocytes in vivo is via liposomes as described above. Clodronate did not deplete CD206-positive renal macrophages and, unlike diphtheria toxin, left resident CD11c-positive cells unscathed while inducing dramatic apoptosis in hepatic and splenic mononuclear phagocyte populations. Transplantation. Similarly, clodronate treatment resulted in significantly reduced acute tubular necrosis. doi: 10.1152/ajprenal.00196.2020. injection of clodronate liposomes, and the population is not restored for 2 wk thereafter . Clodronate molecules are encapsulated in small MLV liposomes for superior activity, physical and chemical stability, and convenience of use. 2021 Jan 18. doi: 10.1038/s41569-020-00489-x. Clipboard, Search History, and several other advanced features are temporarily unavailable. Although either system effectively depleted circulating monocytes and resident mononuclear phagocytes, depletion was most … Van Rooijen, N., & Hendrikx, E. (2010). 2008 Nov 15;86(9):1267-74. doi: 10.1097/TP.0b013e318188d433. We now show that LIP‐CLOD treatment also provoked enhancement of both megakaryocytopoiesis and thrombocytopoiesis. We use cookies to help provide and enhance our service and tailor content and ads. The Journal of Orthopaedic Research, a publication of the Orthopaedic Research Society (ORS), is the forum for the rapid publication of high quality reports of new information on the full spectrum of orthopaedic research, including life sciences, engineering, translational, and clinical studies. Am J Nephrol. administration of 2.5 mg/kg liposome-encapsulated clodronate at a volume of 0.5 ml/kg over a 60-minute period via an indwelling venous catheter, as previously described. into the tail vein 24 h before induction of inflammation. 2020 May 22;21(10):3667. doi: 10.3390/ijms21103667. administration (data not shown). The treatment has been shown to induce selective apoptotic cell death in monocytes/macrophages without affecting lymphocytes and neutrophils (23, 36). Online ahead of print. HHS This result suggests that macrophage depletion is the primary mode of LC action. DT-mediated Mf/monocyte depletion had no effect on renal function 24h after IRI, whereas clodronate treatment induced marked functional protection (Figure 1a). To evaluate mononuclear phagocytic cell effects in our rUUO model of CKD, clodronate or PBS control liposomes were administrated to mice intravenously. The kits come in 2 different varieties: standard kits and mannosylated kits (mainly to target central nervous system). In the current studies, the liposomal clodronate … If clodronate liposomes are being used for complete systemic depletion of macrophages, the rate of repopulation of the phagocytes within the various organs and blood must be taken into account, especially considering that monocyte counts begin to increase between 24-30 hours in mice while liver and splenic macrophages may remain depleted for up to a week or more. Prolonged depletion of Gr1−monocytes was observed. All the authors declared no competing interests. Each Clodrosome Macrophage Depletion Kit contains Clodrosome and an equal volume of control liposomes. Therefore, clodronate liposomes are an excellent tool to study macrophage function [2]. These were prepared as previously described. Abolition of the protected phenotype by administration of diphtheria toxin to clodronate-treated mice suggested that the protective effect of clodronate resulted from the … Mice were injected with clodronate liposomes or PBS liposomes 2 days (0.2 ml iv of liposomes through the tail vein) and 2 h (0.1 ml ip of liposomes) before muscle injury. depletion. Copyright © 2012 International Society of Nephrology. Van Rooijen N, Hendrikx E (2010) Liposomes for specific depletion of macrophages from organs and tissues. Abolition of the protected phenotype by administration of diphtheria toxin to clodronate-treated mice suggested that the protective effect of clodronate resulted from the presence of a cytoprotective intrarenal population of mononuclear phagocytes sensitive to diphtheria toxin-mediated ablation. of skeletal muscle injury using a mouse model and selective depletion of peripheral monocyte with systemic injections of liposomal clodronate (dichloromethylene bisphosphonate). Clophosome ®, neutral clodronate liposomes, offers highly efficient in vivo macrophage depletion. Despite this, diphtheria toxin treatment did not protect from renal ischemia. Macrophage Depletion by Clodronate-Containing Liposomes Reduces Neointimal Formation After Balloon Injury in Rats and Rabbits. Qi F, Adair A, Ferenbach D, Vass DG, Mylonas KJ, Kipari T, Clay M, Kluth DC, Hughes J, Marson LP. However, we have observed in numerous rodent studies that liposomes which contain PBS instead of clodronate solution do not elicit antitumor activity following i.v. Depletion of Monocyte/Macrophages with Clodronate Attenuates CKD in rUUO. After injection, liposomes, used as Trojan horses in this case, will be ingested and digested by macrophages followed by intracellular release and accumulation of clodronate. AM depletion following ITIH delivery of clodronate liposomes was 33.2 ± 14.2 on day 1, 88.1 ± 6.2 on day 3, and 91.4 ± 1.8 on day 4 relative to control rats given saline-containing liposomes. NLM Am J Physiol Renal Physiol. Methods Mol Biol 605:189–203 CrossRef PubMed Google Scholar 3. Stoneman V, Braganza D, Figg N, Mercer J, Lang R, Goddard M, Bennett M. Circ Res. In contrast, mice treated with clodronate exhibited reduced renal failure and acute tubular necrosis, suggesting key differences between these depletion strategies. Additionally, mice were intravenously injected with 100 μl of control liposomes (placebo control liposomes for clophosome-A) or liposomes containing clodronate (clophosome-A-anionic liposomal clodronate for macrophage depletion, FormuMax) the day of occlusion and the two following days leading to a decrease of circulation monocyte population of 84% . Copyright © 2021 Elsevier B.V. or its licensors or contributors. By choosing the right administration route of clodronate liposomes, particular organs or tissues can be depleted of macrophages. To help resolve this, we used mice transgenic for the human diphtheria toxin receptor under the control of the CD11b promoter and treated them with diphtheria toxin, or liposomal clodronate, or both to deplete monocyte/mononuclear phagocytes prior to renal ischemia/reperfusion injury. Female C57Bl/6 mice were given 0.05 U bleomycin (B) intratracheally on Day 0 ± liposomal clodronate (LC) intraperitoneally on Days 21, 22, and 23 and culled on Day 24 (A–C, F–H, and K–M), Day 25 (I, J, S, and T), or Day 28 (A, D, E, K, and N–R). Liposomes for specific depletion of macrophages from organs and tissues. Clodronate-liposome administration resulted in depletion of CD169+ bone marrow–resident macrophages. Nihon Saikingaku Zasshi. Liposomal clodronate was prepared as described previously. Leong KG, Ozols E, Kanellis J, Nikolic-Paterson DJ, Ma FY. Clodronate did not deplete CD206-positive renal macrophages and, unlike diphtheria toxin, left resident CD11c-positive cells unscathed while inducing dramatic apoptosis in hepatic and splenic mononuclear phagocyte populations.  |  Mononuclear phagocyte depletion strategies in models of acute kidney disease: what are they trying to tell us? In the current studies, the liposomal clodronate … Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques. Macrophage depletion can be achieved with the systemic injection of liposomes containing clodronate.6 Clodronate be-longs to the family of bisphosphonates (BPs), bone-seeking agents that are potent inhibitors of osteoclasts. FormuMax proudly offers two types of clodronate liposomes.  |  After Clodrosome has been dosed to the animal by the chosen route, the clodronate liposomes will come into contact with macrophages and other phagocytic cells. This site needs JavaScript to work properly. the liposomes (31, 36). Tumour-associated macrophages, TAMs, play a pivotal role in tumour growth and metastasis by promoting tumour angiogenesis. Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise Noriaki Kawanishia,b, Tsubasa Mizokamic, Hiroyuki Niiharac, Koichi Yadac, Katsuhiko Suzukid,n a Institute for Nanoscience & Nanotechnology, Waseda University, Tokyo, Japan b Research Fellow of the Japan Society for the Promotion of Sciences, Tokyo, Japan Circulation, 2002. - Clodronate Liposomes (intravenous injection). Research output: Contribution to journal › Article Kim DJ, Moon JY, Kim SM, Seo JW, Lee YH, Jung SW, Kim K, Kim YG, Lim SJ, Lee S, Son Y, Lee SH. It is formulated to exceptionally high clodronate/lipid ratio and the encapsulation efficiency of clodronate is above 90%. To help resolve this, we used mice transgenic for the human diphtheria toxin receptor under the control of the CD11b promoter and treated them with diphtheria toxin, or liposomal clodronate, or both to deplete monocyte/mononuclear phagocytes prior to renal ischemia/reperfusion injury. The first step in this destruction is phagocytosis in which the liposomes are engulfed by the cell into an internal vesicle … Clodronate is a first-generation bisphosphonate which, when encapsulated within liposomes, is able to enter phagocytic cells and initiate apoptosis [18– 22]. … [35,36] Dogs were treated by i.v. To help resolve this, we used mice transgenic for the human diphtheria toxin receptor under the control of the CD11b promoter and treated them with diphtheria toxin, or liposomal clodronate, or both to deplete monocyte/mononuclear phagocytes prior to renal ischemia/reperfusion injury. Clodronate induced a 80%-90% depletion of monocyte but only led to 57% and 41% decrease of M1 and M2 macrophage accumulation, respectively, 2 d following injury. Substance P Improves Renal Ischemia Reperfusion Injury Through Modulating Immune Response. Interestingly, this treatment caused a delayed disappearance (7-21 days post injection) of macrophages and … Animals received DT, clodronate, or saline injection 24 h before IRI surgery to assess the functional outcome of Mφ depletion. Liposome encapsulated clodronate induces apoptosis in cells that endocytose the liposomes. Clodronate did not deplete CD206-positive renal macrophages and, unlike diphtheria toxin, left resident CD11c-positive cells unscathed while inducing dramatic apoptosis in hepatic and splenic mononuclear phagocyte populations. Empty liposomes in PBS were used as controls. By continuing you agree to the use of cookies. Conversely, the number of M1 macrophages in monocyte-depleted rats was 2.4-fold higher than in non-depleted rats 4 d after injury. Flow cytometric analysis revealed that clodronate-liposome pretreatment impaired myeloma plasma cell homing and retention within the bone marrow 24 hours postmyeloma plasma cell inoculation. 1. DT-mediated Mφ/monocyte depletion had no effect on renal function 24 h after IRI, whereas clodronate treatment induced marked functional protection . Lu L, Faubel S, He Z, Andres Hernando A, Jani A, Kedl R, Edelstein CL. Encapsome® is formulated and prepared identically to Clodrosome® except that clodronate is not added to the liposomes. 2020;51(11):891-902. doi: 10.1159/000511260. Monocyte Depletion. “Inflammatory” monocyte depletion affects alternatively activated lung macrophages. 3.2. The failure of LC administration to induce monocytopenia in dogs in the present study was unexpected, based on the … The role of resident renal mononuclear phagocytes in acute kidney injury is controversial with experimental data suggesting both deleterious and protective functions. Like other BPs, clodronate has poor cell membrane permeability.7 Liposomes Clodronate (Sifavitor) and rhodamine RE (Avanti Polar Lipids) were encapsulated in liposomes composed of 50 μmol/L distearoyl-phosphatidylglycerol (DSPG) (Avanti), 100 μmol/L cholesterol (Sigma Chemicals), and 150 μmol/L of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) (Avanti) by reverse-phase evaporation technique, as described elsewhere. Springer Nature is developing a new tool to find and evaluate Protocols. 1993 Sep;48(5):685-92. doi: 10.3412/jsb.48.685. This pharmacological treatment has been demonstrated to induce specific apoptotic death in monocytes and phagocytic macrophages. Depletion of Monocyte/Macrophages with Clodronate Attenuates CKD in rUUO. The presence of macrophages in the ovary has been established for many years; however, the precise f… In contrast, mice treated with clodronate exhibited reduced renal failure and acute tubular necrosis, suggesting key differences between these depletion strategies. Surprisingly, depletion of hematogenous macrophages by clodronate liposomes did not improve outcomes 6 days after MCAO, but even increased mortality (Figure 2A; log-rank (Mantel-Cox) test, P=0.001). Clodronate is not a toxic drug in itself and liposomes (if prepared of phosphatidylcholine and cholesterol) are not toxic either.. Free Clodronate will not easily pass phospholipid bilayers of liposomes and cell membranes but liposomes are eagerly swallowed by macrophages.. The study evaluates the influence of monocytes/macrophages in the mechanisms of skeletal muscle injury using a mouse model and selective depletion of peripheral monocyte with systemic injections of liposomal clodronate (dichloromethylene bisphosphonate). m-Clodrosome ® (Liposomal Clodronate) 2012;35(2):181-90. doi: 10.1159/000335582. 9 The average size of liposomes … Engel JE, Williams ML, Williams E, Azar C, Taylor EB, Bidwell GL, Chade AR. The procedure is well tolerated, and its therapeutic potential is currently under investigation. Depletion of cells of monocyte lineage prevents loss of renal microvasculature in murine kidney transplantation. In contrast, DT treatment did not ameliorate the acute tubular necrosis score (Figure In contrast, mice treated with clodronate exhibited reduced renal failure and acute tubular necrosis, suggesting key differences between these depletion strategies. Macrophage depletion by clodronate liposomes also reduced intimal hyperplasia, the. NIH in many studies to deplete monocyte-derived cell populations.11–13 Clodronate is a non-nitrogenous bisphosphonate. Primary goals were to address both the immunohistologic and potential toxic effects of this approach. Kidney Int. By this approach, i.e. Their roles may include the phagocytosis and degradation of foreign organisms, tissue remodeling, and the regulation of local immune and inflammatory responses. Previously, we demonstrated that specific macrophage depletion, using liposomal‐encapsulated clodronate (LIP‐CLOD), induced a rapid recovery of the platelet count in a mouse model of immune thrombocytopenia. Clophosome ®, neutral clodronate liposomes, offers highly efficient in vivo macrophage depletion. Clodronate (200 μ g) or vehicle (PBS control) liposomes were administrated to mice intravenously starting 6 days prior to UUO and continuing every 3-4 days until 10 days after release of obstruction (i.e., animals were … Injection of liposomes. Clodronate-liposome administration resulted in depletion of CD169 + bone marrow–resident macrophages. Clodronate has an extremely short half-life in the circulation and therefore is not toxic. 2007 Dec;28(12):525-31. doi: 10.1016/j.it.2007.08.011. So, depletion of monocytes from the circulation by injections of clodronate liposomes, repeated at shorter time intervals (e..g. two days), are needed for an effective depletion of mature macrophages and dendritic cells in organs where liposomes have no direct access to mature macrophages. depletion improved functional and structural outcomes after stroke. Blood and ankle cells were harvested at days 1, 2, and 3 and were characterized by flow cytometry. Micron sized liposomes engineered specifically to target macrophages in different tissues and organs. Epub 2007 Feb 22.  |  [35,36] Dogs were either treated once weekly (n = 11) or once every two weeks (n = 2) for a total of six or four treatments, respectively. Thus, CLD-lip treatment preferentially targets monocytes and monocyte-derived cells such as macrophages and osteoclasts. The role of resident renal mononuclear phagocytes in acute kidney injury is controversial with experimental data suggesting both deleterious and protective functions. Recovery of Renal Function following Kidney-Specific VEGF Therapy in Experimental Renovascular Disease. Would you like email updates of new search results? Depletion of macrophages and dendritic cells in ischemic acute kidney injury. Clophosome ®, neutral clodronate liposomes, offers highly efficient in vivo macrophage depletion. Control mice received the same dose of PBS liposomes. Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis. Nat Rev Cardiol. Am J Nephrol. J Immunol Methods 174:83–93 CrossRef PubMed Google Scholar 25 After warming and resuspension of the liposomes, a dose of 200 μl was administered intravenously to induce macrophage depletion. eCollection 2020. COVID-19 is an emerging, rapidly evolving situation. Please enable it to take advantage of the complete set of features! Although clodronate liposomes are a well-established method of macrophage depletion in the colon (41, 42, 48), we wanted to confirm successful depletion in our hands and further establish whether it was effective at depleting macrophages in the tumor microenvironment. Selective elimination of activated Mɸs by apoptosis may explain both therapeutic efficacy and safety of clodronate‐liposomes in experimental models … Clodronate reduced circulating total monocyte count by 76% after 24 h (Figure 4i), with recovery evident at 48 h. Both Gr1+and Gr1−subsets were equally depleted at 24 h. Inflammatory Gr1+monocytes rebounded to higher than control levels at 48 h (Figure 4i). Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise Noriaki Kawanishia,b, Tsubasa Mizokamic, Hiroyuki Niiharac, Koichi Yadac, Katsuhiko Suzukid,n a Institute for Nanoscience & Nanotechnology, Waseda University, Tokyo, Japan b Research Fellow of the Japan Society for the Promotion of Sciences, Tokyo, Japan Clodronate molecules are encapsulated in small LUV liposomes for superior activity, physical and chemical stability, and convenience of use. C57BL/6 WT mice were pretreated with clodronate liposomes (clod) for monocyte depletion or control liposomes (control) and subsequently underwent the anti-GBM Ab model. This was attributed in part to decreased levels of macrophage-derived insulin-like growth … See the link below for large selection of macrophage/monocyte depletion kits and reagents (Clodronate liposomes and control liposomes) in various volumes and compositions: Further details on each reagent is available by clicking on “More Info” below its image. Epub 2007 Oct 26. Although either system effectively depleted circulating monocytes and resident mononuclear phagocytes, depletion was most marked in diphtheria toxin-treated mice. In vivo monocyte and synovial macrophage depletion. Int J Mol Sci. Liposome‐encapsulated clodronate and liposome‐encapsulated alendronate decreased total viability of J774 cells but did not ... Leena EL-Mufti, Honglei Ren, Jian Wang, Microglial Depletion with Clodronate Liposomes Increases Proinflammatory Cytokine Levels, Induces Astrocyte Activation, and Damages Blood Vessel Integrity , Molecular Neurobiology, 10.1007/s12035-019-1502-9, (2019). Clodrosome® is a multilamellar liposome suspension in which clodronate is encapsulated in the aqueous compartments of the liposomes. Van Rooijen N, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications.

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