Neutrophils—A Key Component of Ischemia-Reperfusion Injury

Schofield, Zoe; Woodruff, Trent M.; Halai, Reena; Wu, Mike C. L.; Cooper, Matthew A.

doi:10.1097/shk.0000000000000044

Cited by 203 publications

(169 citation statements)

References 97 publications

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“…After measured the cfDNA concentration in serum ( Figure 3D), we found out that in liver IRI mice, the cfDNA concentration in mice treated with Neutrophils are vital for inflammation response [37,38] and play critical roles in IRI. During IRI, blood neutrophilia and neutrophil tissue infiltration are frequently observed [39]. Thus, we assessed the dynamics of neutrophil (Ly6G + ) proportion in the blood ( Figure 3E) and the neutrophil (Ly6G + ) infiltration in liver ( Figure 3F) after IRI.…”

Section: Macrophages/monocytes Were Specifically Targeted By Fasudil mentioning

confidence: 99%

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

et al. 2018

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Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure.During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension.Here, using Fasudil carried liposomes, we specifically inhibited the ROCK-II expression in Kupffer cells and blood monocytes. Through this macrophage/monocyte specific treatment of Fasudil, we successfully protected the liver from IRI by shifting Kupffer cells/monocytes from M1/classical to M2/patrolling phenotype in the liver and peripheral blood. Our finding provides novel insights into the macrophage/monocyte-specific drug delivery and the treatment of liver IRI.

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Section: Macrophages/monocytes Were Specifically Targeted By Fasudil mentioning

confidence: 99%

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

et al. 2018

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“…Tissue injury also directly activates the complement system, leading to the generation of the peptides C5a and C3a (31). The role for C5a in the progression of this pathology is both very well understood and unambiguous; C5a functions at the level of injury to cause extravasation and degranulation of the circulating neutrophils (55). By direct contrast, we demonstrated in a model of intestinal IR that the role for C3a in this acute pathology is overwhelmingly anti-inflammatory (32).…”

Section: C3a In Diseasementioning

confidence: 75%

Is the Complement Activation Product C3a a Proinflammatory Molecule? Re-evaluating the Evidence and the Myth

Coulthard

Woodruff

2015

The Journal of Immunology

251

200

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The complement activation product C3a is often described as a proinflammatory mediator, alongside its downstream cousin, C5a. However, emerging studies show that C3a has several anti-inflammatory facets in vivo. For example, in the acute inflammatory response, C3a acts in direct opposition to C5a, through preventing the accumulation of neutrophils in inflamed tissues by independently regulating their mobilization. This acute, protective, and opposing activity of C3a to C5a is also illustrated in models of septicemia. In this article, we reinvestigate the discovery and original classification of C3a as a proinflammatory mediator and highlight the emerging studies demonstrating anti-inflammatory effects for C3a in the immune response. It is our hope that this review illuminates these apparently contradictory roles for C3a and challenges the general dogma surrounding C3a, which, historically, has ubiquitously been described as a proinflammatory mediator. In light of this, we urge investigators to use “inflammatory modulator” as the descriptor for C3a.

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“…The partial blood supply in the penumbra activates endothelial cells to localize a tremendous neutrophil and macrophage influx [10,16]. Microglia are activated within minutes in injured stroke tissue [17], and, unlike in the stroke core, survive [10].…”

Section: Peri-infarct Tissuementioning

confidence: 99%

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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Stroke not only causes initial cell death, but also a limited process of repair and recovery. As an overall biological process, stroke has been most often considered from the perspective of early phases of ischemia, how these inter-relate and lead to expansion of the infarct. However, just as the biology of later stages of stroke becomes better understood, the clinical realities of stroke indicate that it is now more a chronic disease than an acute killer. As an overall biological process, it is now more important to understand how early cell death leads to the later, limited recovery so as develop an integrative view of acute to chronic stroke. This progression from death to repair involves sequential stages of primary cell death, secondary injury events, reactive tissue progenitor responses, and formation of new neuronal circuits. This progression is radial: from the tissue that suffers the infarct secondary injury signals, including free radicals and inflammatory cytokines, radiate out from the stroke core to trigger later regenerative events. Injury and repair processes occur not just in the local stroke site, but are also triggered in the connected networks of neurons that had existed in the stroke center: damage signals are relayed throughout a brain network. From these relayed, distributed damage signals, reactive astrocytosis, inflammatory processes, and the formation of new connections occur in distant brain areas. In short, emerging data in stroke cell death studies and the development of the field of stroke neural repair now indicate a continuum in time and in space of progressive events that can be considered as the 3 Rs of stroke biology: radial, relayed, and regenerative.

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Neutrophils—A Key Component of Ischemia-Reperfusion Injury

Cited by 203 publications

References 97 publications

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

WITHDRAWN: Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization

Is the Complement Activation Product C3a a Proinflammatory Molecule? Re-evaluating the Evidence and the Myth

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

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