scholarly journals A murine model for study of anticryptococcal activity mediated by cytotoxic immune cells: Role in immunization and human vaccine strategies

2011 ◽  
Vol 61 (2-3) ◽  
pp. 109-118
Author(s):  
Valentina Arsic-Arsenijevic ◽  
Ljubica Petkovic ◽  
A. Dzamic ◽  
Ivana Colovic ◽  
Aleksandra Barac ◽  
...  
Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5671-5671
Author(s):  
John P Galvin ◽  
Sara A Beddow ◽  
Stephen Miller

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapy for hematologic malignancies. The success of allo-HSCT is often limited by acute graft versus host disease (AGVHD), which is a severe and often fatal complication. AGVHD is characterized by production of inflammatory mediators and recruitment and activation of immune cells accounting for damage to target organs including the liver, intestine, and skin. There are a limited number of therapies to treat aGVHD. Steroids remains the mainstay of treatment. The addition of other immunosuppressive agents have shown limited benefit and often increase the potential for life-threatening infections. Inflammatory monocytes are among the immune cells that are recruited to target organs during AGVHD. Inflammatory monocyte involvement in AGVHD has been described both in terms of their innate immune function and in their role in the activation and proliferation of T-cells by antigen presentation and cytokine secretion. Inflammatory monocyte-derived effector cells play an important role in the pathogenesis of numerous inflammatory diseases. Furthermore, clinical studies have reported that monocyte infiltration was correlated directly with AGVHD severity. Despite the importance of inflammatory monocytes in AGVHD, there are no treatments that specifically target these cells. Immune-modifying microparticles (IMPs), derived from biodegradable poly(lactic-co-glycolic) acid (PLGA) have been shown to be taken up by inflammatory monocytes. Subsequently, these monocytes no longer traffic to sites of inflammation; rather, IMP infusion causes their sequestration in the spleen through apoptotic cell clearance. Previous studies have shown that the administration of IMPs in murine models of myocardial infarction, colitis, peritonitis, and encephalitis markedly reduced monocyte accumulation at inflammatory foci, reduced disease symptoms, and promoted tissue repair. Therefore, we hypothesized that the administration of IMPs may reduce clinical symptoms and mortality in a murine model of AGVHD. Methods Murine AGVHD model: BALB/c mice were given 800 cGy total body irradiation, irradiated BALB/c mice were transplanted with 5×106 C57BL/6 bone marrow cells and 1×106 C57BL/6 spleen cells via tail vein. IMP made with PLGA (Phosphorex Inc, Hopkinton MA) was administered to the recipient mice (1.4 mg/kg body weight) by IV daily starting from day 5 to day 10 after bone marrow transplantation (BMT). PBS at the same volume was used as vehicle control. AGVHD monitoring: Mice were individually scored three times a week for five clinical parameters (posture, activity, fur, skin and weight loss) on a scale from 0 to 2. Clinical GVHD score was assessed by summation of these parameters. Survival was monitored daily. AGVHD experiments were performed with at least five mice per group. AGVHD histology: Tissue samples were cryo-embedded and blinded for transplant conditions. Histopathological score was assessed on H&E-stained sections. Results IMPs treated mice had significantly less AGVHD (average score of 2.48) than the untreated BM+Sp group (average score 3.96) starting at the time of IMP treatment (days 5-10) and remained with significantly reduced symptoms of AGVHD for the 30 day course (Figure 1). IMPs treatment also rescued BM+Sp mice from lethal AGVHD with a 30 day overall survival of 62% compared to 4% in the untreated BM+Sp group (Figure 2). Intestinal tissue from the IMPs treated mice compared to the BM+Sp mice demonstrated less evidence of AGVHD (an average score of 1.25 and 2.75, respectively). Hepatic tissue from the IMPs treated mice compared to the BM+Sp mice demonstrated less evidence of AGVHD (an average score of 1.5 and 2.42, respectively) (Figure 3). IMPs treatment significantly reduced INF-𝞬 levels in the intestinal tissues of treated mice compared to untreated BM+Sp mice. Conclusions Our results demonstrate that IMPs significantly reduce symptoms and mortality in a murine model of AGVHD. The reduction in circulating inflammatory monocytes in this model also reduced hepatic lymphocyte infiltration and intestinal mucosal denudation. These findings highlight the potential of IMP therapy as a specific, safe, and cost-effective tool for inhibiting inflammatory monocyte-mediated pathology in AGVHD. Disclosures No relevant conflicts of interest to declare.


2011 ◽  
Vol 59 (10) ◽  
pp. 5299-5304 ◽  
Author(s):  
Micaela Medrano ◽  
Silvia M. Racedo ◽  
Ivanna S. Rolny ◽  
Analía G. Abraham ◽  
Pablo F. Pérez

1997 ◽  
Vol 41 (3) ◽  
pp. 706-708 ◽  
Author(s):  
T Luna ◽  
R Mazzolla ◽  
G Romanò ◽  
E Blasi

A new member of the polyene family, N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diaspartate (SPA), was investigated and was found to be more effective than amphotericin B (i) in vivo by enhancing mouse resistance to cryptococcal meningoencephalitis and (ii) in vitro by potentiating the anticryptococcal activity of murine microglial cells.


2021 ◽  
Vol 22 (22) ◽  
pp. 12170
Author(s):  
Melissa Payet ◽  
Farouk Dargai ◽  
Philippe Gasque ◽  
Xavier Guillot

The inflammatory reaction in rheumatoid arthritis (RA) is controlled by major epigenetic modifications that modulate the phenotype of synovial and immune cells. The aim of this work was to perform a systematic review focusing on miR expression, DNA methylation and histone modifications in RA. We demonstrated that, in human samples, the expressions of miR-155, miR-146a and miR-150 were significantly decreased while the expression of miR-410-3p was significantly increased in the RA group. Moreover, miR-146a significantly decreased pro-autoimmune IL-17 cytokine expression in RA. In a murine model, miR-34a inhibition can ameliorate the arthritis score. However, this evidence remain critically insufficient to support current therapeutic applications in RA patients.


2005 ◽  
Vol 55 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Masood A. Khan ◽  
Rukhsana Jabeen ◽  
T. H. Nasti ◽  
Owais Mohammad

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