C1 inhibitor prevents Gram-negative bacterial lipopolysaccharide-induced vascular permeability

Li, Dongxu; Zhang, Dong; Scafidi, Jennifer; Wu, Xiao Jie; Cramer, Cort C.; Davis, Alvin E.

doi:10.1182/blood-2004-05-1963

Cited by 46 publications

(24 citation statements)

References 42 publications

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“…Chronic intermittent hypoxia/reoxygenation is characteristic of CIH, and several studies support the notion that complement activation is involved in the pathogenesis of hypoxia/reoxygenation injury, and that complement inhibition reduces the extent of injury (5,8,9). In support of this hypothesis, studies have demonstrated that the localization/deposition of complement components (such as C1q, C3, C4 and C5) occurs in hypoxic myocardium (10)(11)(12)(13).…”

Section: Discussionsupporting

confidence: 51%

“…CIH has been suggested to negatively affect left ventricular function, and oxidative stress has been recognized as an important mediator for myocardial damage during this pathophysiological process (8). The major observation made within the current study was that C1INH supplementation during CIH preserved myocardial function, and attenuated myocardial apoptosis through the inhibition of complement activity.…”

Section: Discussionmentioning

confidence: 48%

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C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury

Guo

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The optimal treatment for chronic intermittent hypoxia (CIH)-induced cardiovascular injuries has yet to be determined. The aim of the current study was to explore the potential protective effect and mechanism of a C1 inhibitor in CIH in the myocardium. The present study used a rat model of CIH in which complement regulatory protein, known as C1 inhibitor (C1INH), was administered to the rats in the intervention groups. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The expression of proteins associated with the apoptotic pathway, such as B-cell lymphoma 2 (Bcl-2), Bax and caspase-3 were detected by western blot analysis. The expression of complement C3 protein and RNA were also analyzed. C1INH was observed to improve the cardiac function in rats with CIH. Myocardial myeloperoxidase activity, a marker of neutrophil infiltration, was significantly decreased in the C1INH intervention group compared with the CIH control group, and cardiomyocyte apoptosis was significantly attenuated (P<0.05). Western blotting and reverse transcription-polymerase chain reaction analysis indicated that the protein expression levels of Bcl-2 were decreased and those of Bax were increased in the CIH group compared with the normal control group, but the protein expression levels of Bcl-2 were increased and those of Bax were decreased in the C1INH intervention group, as compared with the CIH group. Furthermore, the CIH-induced expression and synthesis of complement C3 in the myocardium were also reduced in the C1INH intervention group. C1INH, in addition to inhibiting complement activation and inflammation, preserved cardiac function in CIH-mediated myocardial cell injury through an anti-apoptotic mechanism.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 48%

C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury

Guo

Chen

et al. 2016

Experimental and Therapeutic Medicine

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“…Our data indicated that not only did intact, active C1 inhibitor protect from endotoxin shock, but that treatment with inactive, reactive center cleaved C1 inhibitor also was effective (Liu et al, 2003). Both active and inactive C1 inhibitor also prevented both local and systemic vascular permeability changes in response to endotoxin (Liu et al, 2005b). C1 inhibitor prevented the binding of Salmonella typhimurium LPS to the murine macrophage cell line, RAW 264.7, and to human blood cells.…”

Section: The Interaction Of C1 Inhibitor With Gram Negative Bacterialmentioning

confidence: 65%

“…Initial data suggest that, in some instances, these reactions may be significant contributors to the anti-inflammatory activity of this important protease inhibitor. These include at least four different binding reactions (Table 2): (1) An interaction with a variety of extracellular matrix components (Patston and Schapira, 1997); (2) inhibition of alternative complement pathway activation via binding of C1 inhibitor to C3b which prevents its interaction with factor B, in a manner analogous to that of factor H (Jiang et al, 2001); (3) an interaction with both E and P selectins on endothelial cells that is mediated by one or more Lewis x tetrasaccharides expressed on C1 inhibitor, and which results in suppression of leukocyte rolling and transmigration Cai et al, 2005); (4) binding to endotoxin from several different gram negative bacteria that results in suppression of endotoxin shock by interference with the interaction of endotoxin with its receptor complex on macrophages (Liu et al, 2003;Liu et al, 2004;Liu et al, 2005a;Liu et al, 2005b); (5) direct binding to gram negative bacteria that results in suppression of the development of sepsis (unpublished data). This review will briefly summarize the limited information available on the first two reactions and will describe in more detail the data relating to the interactions with selectins and with endotoxin lipopolysaccharide (LPS).…”

Section: Introductionmentioning

confidence: 99%

C1 inhibitor: Biologic activities that are independent of protease inhibition

Davis

Cai

2007

Immunobiology

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C1 inhibitor therapy improves outcome in several animal models of inflammatory disease. These include sepsis and gram negative endotoxin shock, vascular leak syndromes, hyperacute transplant rejection, and ischemia-reperfusion injury. Furthermore, some data suggest a beneficial effect in human inflammatory disease. In many inflammatory conditions, complement system activation plays a role in pathogenesis. The contact system also very likely is involved in mediation of damage in inflammatory disease. Therefore, the beneficial effect of C1 inhibitor has been assumed to result from inhibition of one or both of these systems. Over the past several years, several other potential anti-inflammatory effects of C1 inhibitor have been described. These effects do not appear to require protease inhibition and depend on non-covalent interactions with other proteins, cell surfaces or lipids. In the first, C1 inhibitor binds to a variety of extracellular matrix components including type IV collagen, laminin, entactin and fibrinogen. The biologic role of these reactions is unclear, but they may serve to concentrate C1 inhibitor at extravascular inflammatory sites. The second is a noncovalent interaction with C3b that results in inhibition of formation of the alternative pathway C3 convertase, a function analogous to that of factor H. The third is an interaction with E and P selectins on endothelial cells that is mediated by the Lewis x tetrasaccharides that are expressed on C1 inhibitor. These interactions result in suppression of leukocyte rolling and transmigration. The fourth interaction is the binding of C1 inhibitor to gram negative bacterial endotoxin that results in suppression of endotoxin shock by interference with the interaction of endotoxin with its receptor complex on macrophages. Lastly, C1 inhibitor binds directly to gram negative bacteria, which leads to suppression of the development of sepsis, as demonstrated in the cecal ligation and puncture model. These observations suggest that C1 inhibitor is a multi-faceted anti-inflammatory protein that exerts its effects through a variety of mechanisms including both protease inhibition and several different non-covalent interactions that are unrelated to protease inhibition.

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“…41 To analyze the contribution of VSMCs TF to the activation of coagulation, TF flox/flox ,SM22␣ Cre mice were generated using mice expressing Cre recombinase under control of the VSMC-specific promoter SM22␣. The SM22␣ promoter is expressed in VSMCs in major arteries.…”

Section: Selective Deletion Of Tf Gene In Either Ecs or Vsmcs Does Nomentioning

confidence: 99%

Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice

Pawliński

Wang

Owens

et al. 2010

Blood

158

157

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C1 inhibitor prevents Gram-negative bacterial lipopolysaccharide-induced vascular permeability

Cited by 46 publications

References 42 publications

C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury

C1 inhibitor-mediated myocardial protection from chronic intermittent hypoxia-induced injury

C1 inhibitor: Biologic activities that are independent of protease inhibition

Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice

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