Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from Aortic Macrophages

ABSTRACT: Normal arteries contain a large population of tissue resident macrophages (MÎ¦). Their origins, as well as the mechanisms that sustain them during homeostasis and disease, however, are poorly understood. Gene expression profiling, we show, identifies arterial MÎ¦ as a distinct population among tissue MÎ¦. Ontologically, arterial MÎ¦ arise before birth, though CX3CR1-, Csf1r-, and Flt3-driven fate mapping approaches demonstrate MÎ¦ colonization occurs through successive contributions of yolk sac (YS) and conventional hematopoiesis. In adulthood, arterial MÎ¦ renewal is driven by local proliferation rather than monocyte recruitment from the blood. Proliferation sustains MÎ¦ not only during steady state conditions, but mediates their rebound after severe depletion following sepsis. Importantly, the return of arterial MÎ¦ to functional homeostasis after infection is rapid; repopulated MÎ¦ exhibit a transcriptional program similar to resting MÎ¦ and efficiently phagocytose bacteria. Collectively, our data provide a detailed framework for future studies of arterial MÎ¦ function in health and disease. Aortic macrophages (CD11bhighF4/80highCD45+MerTK+CD64+) were isolated from C57/B6 wild-type male mice aged 6-8 weeks before and 7 days after induction of sepsis by cecal puncture. 18-20 aortas were pooled per sample. Each condition contained three biological replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Clint Robbins

PROVIDER: E-GEOD-68968 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis. While several studies have reported the proteomic alteration in plasma, urine, heart, etc. of sepsis, few research focused on the brain tissue. This study aims at discovering the differentially abundant proteins in the brains of septic rats to identify biomarkers of SAE. Methods: The Prague-Dawley rats were randomly divided into sepsis (n = 6) or sham (n = 6) groups, and then the whole brain tissue was dissected at 24 h after surgery for further protein identification by TMT-LC–MS/MS-based proteomics. Ingenuity pathway analysis, Gene ontology knowledgebase, and STRING database are used to explore the biological significance of proteins with altered concentration. Results: Among the total of 3163 proteins identified in the brain tissue, 57 were increased while 38 were decreased in the sepsis group compared to the sham group. Bioinformatic analyses suggest that the differentially abundant proteins are highly related to cellular microtubule metabolism, energy production, nucleic acid metabolism, neurological disease, etc. Additionally, acute phase response signaling was possibly activated and PI3K/AKT signaling was suppressed during sepsis. An interaction network established by IPA revealed that Akt1, Gc-globulin, and ApoA1 were the core proteins. The increase of Gc-globulin and the decrease of Akt1 were confirmed by Western blot. Conclusions: Based on the multifunction of these proteins in several brain diseases, we first propose that Gc-globulin, ApoA1, PI3K/AKT pathway, and acute phase response proteins (hemopexin and cluster of alpha-2-macroglobulin) can potentially be diagnosis biomarkers, therapeutic targets, and prognosis indicators of SAE. These results may provide new insights into the pathologic mechanism of SAE, yet further research is required to explore the functional implications and clinical applications of the differentially abundant proteins in the brains of sepsis group.

Project description:Our experiments examined T-lymphocyte numbers and effector-functions in peritoneal contamination and infection (PCI) a mouse model of sepsis. One of our main questions was how T-lymphocytes reconstitute after sepsis-induced lymphopenia. We investigated the quantitative and qualitative recovery of T lymphocytes for 3.5 months after sepsis with or without IL-7 treatment. Sepsis is an immunological dysfunction against pathogens leading to inflammation with massive cytokine production. Simultaneously immunosuppression occurs e.g. lymphopenia, which is a hallmark of sepsis. The resulting immunosuppression is associated with secondary infections, which are often lethal. Moreover sepsis-survivors are burdened with increased morbidity and mortality for several years after the sepsis episode. The duration and clinical consequences of sepsis induced-immunosuppression are currently unknown. More than 50% of T-cells undergo apoptosis shortly after sepsis-induction. However, 8 days after sepsis onset, surviving mice present normal lymphocyte counts. Theoretically, T-cells could reconstitute in two different ways. Firstly, the diminished pool of T-cells is replenished by newly in thymus produced T-cells with new diverse T-cell-receptors (TCRs). Alternatively, remaining T-cells start to proliferate until reaching normal cell count. If this was the case all divided cells shared the same TCRs as primary cells. This could lead to a narrowed TCR diversity within a quantitative normalized T-cell pool and would be an explanation for the long-lasting immune incompetence. To address the question how T-cells recover from lymphopenia we applied next generation sequencing (NGS) to analyse TCR diversity in septic and healthy mice. One group of septic mice received Interleukin-7 (IL-7), an interleukin which regulates T-cell homeostasis and is a promising therapeutically approach for septic patients. 50000 sequences per mouse were analyzed and the three different groups (controls, sepsis, sepsis + IL-7 treatment) compared regarding their diversity. The sequenced raw data (fastq) are uploaded in this library.

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Expression data from Aortic Macrophages

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