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| Flow cytometry of lymphocytes indicate a decreased frequency of GATA3+CD4+ Th2 cells (p = 0.0097), Tregs cells (p = 0.0285) in CD4+ T cells and increased frequency of CD4+ T cell in live splenocytes (p = 0.0268), ratio of Th1/Th2 (p = 0.0287) in Serp-1m5 treated mice compared with saline treated mice while no significant differences in the frequency of NK cells, CD8+ T cells, IFNg+CD4+ Th1 cells, Th17 cells in CD4+ T cells among the three groups. *p < 0.05, **p < 0.01.

| Flow cytometry of lymphocytes indicate a decreased frequency of GATA3+CD4+ Th2 cells (p = 0.0097), Tregs cells (p = 0.0285) in CD4+ T cells and increased frequency of CD4+ T cell in live splenocytes (p = 0.0268), ratio of Th1/Th2 (p = 0.0287) in Serp-1m5 treated mice compared with saline treated mice while no significant differences in the frequency of NK cells, CD8+ T cells, IFNg+CD4+ Th1 cells, Th17 cells in CD4+ T cells among the three groups. *p < 0.05, **p < 0.01.

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Diffuse alveolar hemorrhage (DAH) is one of the most serious clinical complications of systemic lupus erythematosus (SLE). The prevalence of DAH is reported to range from 1 to 5%, but while DAH is considered a rare complication there is a reported 50-80% mortality. There is at present no proven effective treatment for DAH and the therapeutics that...

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... change in detected CD163+ M2 in F4/80+ macrophages, nor in CD11b or CD11c cells in live splenocytes was seen ( Figure 6B). A significant increase in CD4+ T cells in live splenocytes (p = 0.0268) and the TH1/Th2 ratio (p = 0.0287) was detected (Figure 7); A significant decrease in Tregs (p = 0.0285) and GATA3+CD4+ Th2 cells (p = 0.0097) in CD4+ T cells were detected with Serp-1m5 but not the unmodified Serp-1 (Figure 7); There was no significant change in the frequency of NK cells, CD8+ T cells, CD11b+cells, CD11c+ cells in living spleen cells, IFNg+CD4+ Th1 cells, Th17 cells in CD4+ T cells, and CD163+F480+M2 macrophages in F4/80+ macrophages among the three groups (Figures 6, 7). ...
Context 2
... change in detected CD163+ M2 in F4/80+ macrophages, nor in CD11b or CD11c cells in live splenocytes was seen ( Figure 6B). A significant increase in CD4+ T cells in live splenocytes (p = 0.0268) and the TH1/Th2 ratio (p = 0.0287) was detected (Figure 7); A significant decrease in Tregs (p = 0.0285) and GATA3+CD4+ Th2 cells (p = 0.0097) in CD4+ T cells were detected with Serp-1m5 but not the unmodified Serp-1 (Figure 7); There was no significant change in the frequency of NK cells, CD8+ T cells, CD11b+cells, CD11c+ cells in living spleen cells, IFNg+CD4+ Th1 cells, Th17 cells in CD4+ T cells, and CD163+F480+M2 macrophages in F4/80+ macrophages among the three groups (Figures 6, 7). ...

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... Treatment with purified native Serp-1 has demonstrated both acute and long-term efficacy in modulating inflammation in a wide range of inflammatory disorders and injuries, including atherosclerosis, transplant, wound healing, and spinal cord injury [39][40][41][42]. More recently, a modified Serp-1 protein, PEGSerp-1, with a longer halflife (~8 h), was shown to reduce inflammation and fibrosis in healing corneal wounds, and reduced macrophage invasion of alveoli in a mouse model of diffuse alveolar hemorrhage [43][44][45]. Based on these previous studies, we examined whether the pegylated version of the viral Serp-1 protein, PEGSerp-1, would ameliorate the chronic inflammatory pathology of DMD. ...
... Serp-1 was endotoxin-free, as detected by limulus amebocyte lysate (LAL) assay. Serp-1 was incubated with mPEG-NHS (5 K) (Nanocs Inc., #PG1-SC-5k-1, New York, NY, USA) in PBS (pH 7.8) at 4 • C overnight to modify the protein according to standard PEGylation protocols [43]. PEGylated-Serp-1 was purified by FPLC using an ÄKTA pure protein purification system with Superdex-200 [43]. ...
... Serp-1 was incubated with mPEG-NHS (5 K) (Nanocs Inc., #PG1-SC-5k-1, New York, NY, USA) in PBS (pH 7.8) at 4 • C overnight to modify the protein according to standard PEGylation protocols [43]. PEGylated-Serp-1 was purified by FPLC using an ÄKTA pure protein purification system with Superdex-200 [43]. ...
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Duchenne muscular dystrophy is an X-linked disease afflicting 1 in 3500 males that is characterized by muscle weakness and wasting during early childhood, and loss of ambulation and death by early adulthood. Chronic inflammation due to myofiber instability leads to fibrosis, which is a primary cause of loss of ambulation and cardiorespiratory insufficiency. Current standard of care focuses on reducing inflammation with corticosteroids, which have serious adverse effects. It is imperative to identify alternate immunosuppressants as treatments to reduce fibrosis and mortality. Serp-1, a Myxoma virus-derived 55 kDa secreted glycoprotein, has proven efficacy in a range of animal models of acute inflammation, and its safety and efficacy has been shown in a clinical trial. In this initial study, we examined whether pegylated Serp-1 (PEGSerp-1) treatment would ameliorate chronic inflammation in a mouse model for Duchenne muscular dystrophy. Our data revealed a significant reduction in diaphragm fibrosis and increased myofiber diameter, and significantly decreased pro-inflammatory M1 macrophage infiltration. The M2a macrophage and overall T cell populations showed no change. These data demonstrate that treatment with this new class of poxvirus-derived immune-modulating serpin has potential as a therapeutic approach designed to ameliorate DMD pathology and facilitate muscle regeneration.
... A PEGylated version of the Myxomavirus derived SERPIN Serp-1 has also been developed demonstrating improved efficacy in a mouse model of diffuse alveolar hemorrhage (259). Serp-1 is a broad acting SERPIN with anti-inflammatory and antifibrinolytic activities (260). ...
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Appropriate activation of coagulation requires a balance between procoagulant and anticoagulant proteins in blood. Loss in this balance leads to hemorrhage and thrombosis. A number of endogenous anticoagulant proteins, such as antithrombin and heparin cofactor II, are members of the serine protease inhibitor (SERPIN) family. These SERPIN anticoagulants function by forming irreversible inhibitory complexes with target coagulation proteases. Mutations in SERPIN family members, such as antithrombin, can cause hereditary thrombophilias. In addition, low plasma levels of SERPINs have been associated with an increased risk of thrombosis. Here, we review the biological activities of the different anticoagulant SERPINs. We further consider the clinical consequences of SERPIN deficiencies and insights gained from preclinical disease models. Finally, we discuss the potential utility of engineered SERPINs as novel therapies for the treatment of thrombotic pathologies.