Hyperacute rejection of mouse lung by human blood: characterization of the model and the role of complement1

Schröder, Carsten; Wu, Guosheng; Price, Edward; Johnson, Joyce E.; Pierson, Richard N.; Azimzadeh, Agnes M.

doi:10.1097/01.tp.0000069836.91593.09

Cited by 6 publications

(4 citation statements)

References 20 publications

(21 reference statements)

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“…In an ex vivo pig-to-human perfusion model, the survival of C1INH perfused kidneys was significantly longer than controls and the activation of complement, platelets and neutrophils was markedly reduced (70). Similar findings were obtained from other ex vivo transplantation models (71,72). In lung transplantation models, pre-treatment with C1INH prevented early pulmonary dysfunction and organ damage (73,74).…”

Section: Transplantationsupporting

confidence: 76%

C1 inhibitor, a multi-functional serine protease inhibitor

2010

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SummaryC1 inhibitor (C1INH) is a serpin that regulates both complement and contact (kallikrein-kinin) system activation. It consists of a serpin domain that is highly homologous to other serpins and an amino terminal non-serpin mucin-like domain. Deficiency of C1INH results in hereditary angioedema, a disease characterised by episodes of angioedema of the skin or the mucosa of the gastrointestinal tract or the oropharynx. Although early data suggested that angioedema was mediated via complement system activation, the preponderance of the data indicate that bradykinin is the mediator. In the past few years, it has become apparent that C1INH has additional anti-inflammatory functions independent of protease inhibition. These include interactions with leukocytes that may result in enhanced phagocytosis, with endothelial cells via Eand P-selectins that interfere with leukocyte rolling and in turn results in suppression of transmigration of leukocytes across the endothelium, and interactions with extracellular matrix components that may serve to concentrate C1INH at sites of inflammation. In addition, C1INH suppresses gram negative sepsis and endotoxin shock, partly via direct interaction with endotoxin that interferes with its interaction with macrophages, thereby suppressing tumour necrosis factor-α and other inflammatory mediators. C1INH treatment improves outcome in a number of disease models, including sepsis and other bacterial infections, possibly malaria, ischaemia-reperfusion injury (intestinal, hepatic, muscle, cardiac, brain), hyper-acute transplant rejection, and other inflammatory disease models. Recent data suggest that this effectiveness is the result of mechanisms that do not require protease inhibition, in addition to both complement and contact system activation.

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Section: Transplantationsupporting

confidence: 76%

C1 inhibitor, a multi-functional serine protease inhibitor

2010

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“…Complement, platelet and neutrophil activation were reduced in the treated compared with the control kidneys. Similar results were obtained using ex vivo pig lung- or mouse lung-whole human blood models, although injury was not completely prevented (Schelzig et al, 2001; Schroder et al, 2003). In another study, the addition of C1 inhibitor did not further prolong the survival of ex vivo human blood perfused human CD55 transgenic pig lungs (Poling et al, 2006).…”

Section: C1 Inhibitor-mediated Modulation Of Inflammatory Diseasesupporting

confidence: 69%

Biological activities of C1 inhibitor

Davis

Mejia

2008

Molecular Immunology

251

202

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Broadly speaking, C1 inhibitor plays important roles in the regulation of vascular permeability and in the suppression of inflammation. Vascular permeability control is exerted largely through inhibition of two of the proteases involved in the generation of bradykinin, factor XIIa and plasma kallikrein (the plasma kallikrein-kinin system). Anti-inflammatory functions, however, are exerted via several activities including inhibition of complement system proteases (C1r, C1s, MASP2) and the plasma kallikrein-kinin system proteases, in addition to interactions with a number of different proteins, cells and infectious agents. These more recently described, as yet incompletely characterized, activities serve several potential functions, including concentration of C1 inhibitor at sites of inflammation, inhibition of alternative complement pathway activation, inhibition of the biologic activities of gram negative endotoxin, enhancement of bacterial phagocytosis and killing, and suppression of the influx of leukocytes into a site of inflammation. C1 inhibitor has been shown to be therapeutically useful in a variety of animal models of inflammatory diseases, including gram negative bacterial sepsis and endotoxin shock, suppression of hyperacute transplant rejection, and treatment of a variety of ischemia-reperfusion injuries (heart, intestine, skeletal muscle, liver, brain). In humans, early data appear particularly promising in myocardial reperfusion injury. The mechanism (or mechanisms) of the effect of C1 inhibitor in these conditions is (are) not completely clear, but involve inhibition of complement and contact system activation, in addition to variable contributions from other C1 inhibitor activities that do not involve protease inhibition.

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“…Schroeder et al (7) published a study in 2003 in which lungs from male wild-type mice were perfused ex vivo with human blood. After removal of the heart-lung block, the main pulmonary artery was cannulated with an intravenous catheter.…”

Section: Rodent Models-mentioning

confidence: 99%

“…In that case it is possible to place an angiocatheter in the internal jugular vein through the midline surgical tracheostomy. 7 We give a heparin dose of 500 IU/kg.…”

mentioning

confidence: 99%

Xenogeneic Lung Transplantation Models

Burdorf

Azimzadeh

Pierson

2020

Xenotransplantation

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Study of lung xenografts has proven useful to understand the remaining barriers to successful transplantation of other organ xenografts. In this chapter, the history and current status of lung xenotransplantation will be briefly reviewed and two different experimental models, the ex vivo porcine-to-human lung perfusion and the in vivo xenogeneic lung transplantation, will be presented. We will focus on the technical details of these lung xenograft models in sufficient detail, list the needed materials and mention analysis techniques to allow others to adopt them with minimal learning curve.

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Hyperacute rejection of mouse lung by human blood: characterization of the model and the role of complement1

Cited by 6 publications

References 20 publications

C1 inhibitor, a multi-functional serine protease inhibitor

C1 inhibitor, a multi-functional serine protease inhibitor

Biological activities of C1 inhibitor

Xenogeneic Lung Transplantation Models

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