Decay-Accelerating Factor Attenuates C-Reactive Protein-Potentiated Tissue Injury After Mesenteric Ischemia/Reperfusion

Lu, Xinyue; Li, Yansong; Simovic, Milomir O.; Peckham, Russell M.; Wang, Ying; Tsokos, George C.; Lucca, Jurandir J. Dalle

doi:10.1016/j.jss.2009.10.021

Cited by 23 publications

(25 citation statements)

References 43 publications

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“…DAF, a ubiquitously expressed intrinsic complement regulatory protein, inhibits complement activation by preventing the assembly or accelerating the disassembly of the C3/C5 convertases in both the classic and alternative pathways thereby limiting the local C3a/C5a and C5b-9 production [28]. Human DAF has a structure similar to rat DAF and has displayed cross-species reactivity [29].…”

Section: Discussionmentioning

confidence: 99%

Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats

Chavko

Slack

et al. 2013

acta neuropathol commun

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BackgroundBlast-induced neurotrauma (BINT) is the signature life threatening injury of current military casualties. Neuroinflammation is a key pathological occurrence of secondary injury contributing to brain damage after blast injury. We have recently demonstrated that blast-triggered complement activation and cytokine release are associated with BINT. Here, we evaluated if administration of the complement inhibitor recombinant human decay-accelerating factor (rhDAF) is beneficial on neuroinflammation and neurodegeneration in a rat model of moderate BINT. Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood–brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP. These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI.ResultAdministration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood–brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP.ConclusionThese novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI.

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Section: Discussionmentioning

confidence: 99%

Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats

Chavko

Slack

et al. 2013

acta neuropathol commun

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“…In a mesenteric I/R model, CRP deposition correlated with complement deposition, suggesting a role of CRP in complement activation [23]; in these studies, inhibition of complement activation by using C1 inhibitor reduced the effects of CRP on intestinal injury. Similarly, inhibition of complement activation by decay-accelerating factor also prevented CRP-mediated intestinal injury and remote lung damages following mesenteric I/R [24]. In mice transgenic for human CRP, arterial injury resulted in an expedited and higher rate of thrombotic occlusion compared to that in nontransgenic mice [35].…”

Section: Pch-binding Function Of Native Pentameric Crp Myocardialmentioning

confidence: 99%

Recognition Functions of Pentameric C-Reactive Protein in Cardiovascular Disease

Agrawal

Gang

Rusiñol

2014

Mediators of Inflammation

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C-reactive protein (CRP) performs two recognition functions that are relevant to cardiovascular disease. First, in its native pentameric conformation, CRP recognizes molecules and cells with exposed phosphocholine (PCh) groups, such as microbial pathogens and damaged cells. PCh-containing ligand-bound CRP activates the complement system to destroy the ligand. Thus, the PCh-binding function of CRP is defensive if it occurs on foreign pathogens because it results in the killing of the pathogen via complement activation. On the other hand, the PCh-binding function of CRP is detrimental if it occurs on injured host cells because it causes more damage to the tissue via complement activation; this is how CRP worsens acute myocardial infarction and ischemia/reperfusion injury. Second, in its nonnative pentameric conformation, CRP also recognizes atherogenic low-density lipoprotein (LDL). Recent data suggest that the LDL-binding function of CRP is beneficial because it prevents formation of macrophage foam cells, attenuates inflammatory effects of LDL, inhibits LDL oxidation, and reduces proatherogenic effects of macrophages, raising the possibility that nonnative CRP may show atheroprotective effects in experimental animals. In conclusion, temporarily inhibiting the PCh-binding function of CRP along with facilitating localized presence of nonnative pentameric CRP could be a promising approach to treat atherosclerosis and myocardial infarction. There is no need to stop the biosynthesis of CRP.

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“…The pathogenic role of fibrin in thrombosis is well known. CRP has been demonstrated to enhance ischemia/reperfusion injury by activating the complement system (Lu et al, 2009). Elevated serum values of CRP are known to be associated with an increased risk of human atherosclerosis.…”

Section: Diverse Functional Activities Of Acute Phase Proteins (Apps)mentioning

confidence: 99%

Acute Phase Proteins: Structure and Function Relationship

Janciauskiene¹,

Welte²,

Mahadeva³

2011

Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins

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Decay-Accelerating Factor Attenuates C-Reactive Protein-Potentiated Tissue Injury After Mesenteric Ischemia/Reperfusion

Cited by 23 publications

References 43 publications

Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats

Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats

Recognition Functions of Pentameric C-Reactive Protein in Cardiovascular Disease

Acute Phase Proteins: Structure and Function Relationship

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