Inflammatory Models
Sepsis
Sepsis is the most important cause of death among hospitalized patients, with mortality rates ranging from 30 to 70%. Sepsis is the result of an acute and systemic immune response to a variety of noxious insults, in particular to bacterial infection. This response leads to the activation of a number of host mediator systems, including the cytokine, leukocyte, complement and hemostatic network, each of which may contribute to the pathological sequelae of sepsis. Sepsis-associated mortality is highly related to the development of the multi-organ dysfunction syndrome (MODS).
Sepsis - In vivo Models
We use two different mouse models to analyze the development and progression of sepsis-induced multi-organ dysfunction syndrome.
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Injection of lipopolysaccharide (LPS)
model for endotoxemia induced by gram negative organisms
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Cecal Ligation and Puncture (CLP)
model for polymicrobial sepsis
Available Readouts
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Systemic and local inflammatory response
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Cytokine / chemokine profile in serum and peritoneal lavage fluid (PLF)
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Immunophenotyping of peritoneal lavage fluid (PLF): quantitation of macrophages, monocytes, neutrophils, T cells, B cells
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Multi-organ dysfunction syndrome
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clinical chemistry for serum creatinine, BUN, alanine-aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH)
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Renal failure
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Glomerular filtration rate (GFR)
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Renal blood flow (RBF)
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Endothelial injury
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Evan’s blue dye extravasation
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Tissue injury
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Morphology (H&E, Masson Trichrome staining)
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IHC for specific markers of interests
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Apoptosis
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Techniques
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Flow cytometry including Bead-based flow cytometry
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Histology (H&E, Masson Trichrome, Periodic Acid Schiff (PAS) staining)
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Renal function (Inulin and PAH clearance)
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Molecular biology (Real-Time PCR, Western blot)
Need further Readouts? We routinely develop new models to fit our cutomer needs.
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Sepsis - In vitro Models
Sepsis - relevant Publications
Willenberg I, Rund K, Rong S, Shushakova N, Gueler F, Schebb NH, Willenberg I, et al. Inflamm Res. 2016 Feb;65(2):133-42. doi: 10.1007/s00011-015-0897-7. Epub 2015 Dec 8.Inflamm Res. 2016. PMID: 26645911
Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity.
Willenberg I, Meschede AK, Gueler F, Jang MS, Shushakova N, Schebb NH, Willenberg I, et al. PLoS One. 2015 Oct 6;10(10):e0139147. doi: 10.1371/journal.pone.0139147. eCollection 2015.PLoS One. 2015. PMID: 26440517
Hoehlig K, Maasch C, Shushakova N, Buchner K, Huber-Lang M, Purschke WG, Vater A, Klussmann S, Hoehlig K, et al. Mol Ther. 2013 Dec;21(12):2236-46. doi: 10.1038/mt.2013.178. Epub 2013 Jul 26.
David S, Park JK, Meurs Mv, Zijlstra JG, Koenecke C, Schrimpf C, Shushakova N, Gueler F, Haller H, Kümpers P, David S, et al. Cytokine. 2011 Aug;55(2):251-9. doi: 10.1016/j.cyto.2011.04.005. Epub 2011 Apr 30.
Kumpers P, Gueler F, David S, Slyke PV, Dumont DJ, Park JK, Bockmeyer CL, Parikh SM, Pavenstadt H, Haller H, Shushakova N, Kumpers P, et al. Crit Care. 2011;15(5):R261. doi: 10.1186/cc10523. Epub 2011 Oct 31.
Effects of a synthetic PEG-ylated Tie-2 agonist peptide on endotoxemic lung injury and mortality.
David S, Ghosh CC, Kümpers P, Shushakova N, Van Slyke P, Khankin EV, Karumanchi SA, Dumont D, Parikh SM, David S, et al. Am J Physiol Lung Cell Mol Physiol. 2011 Jun;300(6):L851-62. doi: 10.1152/ajplung.00459.2010. Epub 2011 Mar18.
Acute inflammation – Air pouch model
The Air Pouch model offers an accurate, reliable, short-time and inexpensive model to study localized inflammation without systemic effects. An Air Pouch is produced by subcutaneous injection of sterile air into the back of a mouse providing a localized environment for study of anti-inflammatory activity of test compounds and the mechanisms of their action. Local inflammatory challenge induced by injection of an inflammatory stimulus (LPS, IL-1b, C5a) into the air pouch results in pro-inflammatory mediator release and leukocyte extravasation. An inflammatory exudate can be easily collected from air pouch for subsequent analysis.
Available Readouts
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Exudatevolume
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Leukocyte number
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Immunophenotyping of infiltrating leukocytes
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Cytokine/chemokine profile in inflammatory exudate
Techniques
1. Flow cytometry including Bead-based flow cytometry
2. ELISA