Feedback Amplification of Neutrophil Function

Németh, Tamás; Mócsai, Attila

doi:10.1016/j.it.2016.04.002

Cited by 69 publications

(65 citation statements)

References 109 publications

(81 reference statements)

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“…In UC, unrestricted neutrophil activation may cause significant tissue damage that further leads to chronic pathology, whereas in CD, defective neutrophils may not be able to limit invasion by microorganisms, leading to subsequent uncontrolled inflammatory reaction. Each component brought by neutrophils are essential for their normal action, and they can also trigger positive feedback amplification loops that promote neutrophil recruitment and activation, contributing to the pathogenesis of several diseases such as autoimmune and chronic diseases [124,192]. In addition, some neutrophil-derived factors can be detrimental by inducing tissue damage, while they can also be essential to maintain tissue homeostasis.…”

Section: Discussionmentioning

confidence: 99%

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The Dual Role of Neutrophils in Inflammatory Bowel Diseases

Wéra

Lancellotti

Oury

2016

JCM

215

185

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Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of immunity, clearly separate them. Neutrophils are the first immune cells recruited to the site of inflammation, and their action is crucial to limit invasion by microorganisms. Furthermore, they play an essential role in proper resolution of inflammation. When these processes are not tightly regulated, they can trigger positive feedback amplification loops that promote neutrophil activation, leading to significant tissue damage and evolution toward chronic disease. Defective chemotaxis, as observed in Crohn’s disease, can also contribute to the disease through impaired microbe elimination. In addition, through NET production, neutrophils may be involved in thrombo-embolic events frequently observed in IBD patients. While the role of neutrophils has been studied in different animal models of IBD for many years, their contribution to the pathogenesis of IBD remains poorly understood, and no molecules targeting neutrophils are used and validated for the treatment of these pathologies. Therefore, it is crucial to improve our understanding of their mode of action in these particular conditions in order to provide new therapeutic avenues for IBD.

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Section: Discussionmentioning

confidence: 99%

“…Besides MMPs, neutrophils release a lot of extracellular mediators that amplify neutrophil response in an autocrine and paracrine manner [124]. During their activation, neutrophils produce several cytokines and chemokines [125].…”

Section: Role Of Neutrophil-derived Moleculesmentioning

confidence: 99%

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

Wéra

Lancellotti

Oury

2016

JCM

215

185

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“…Neutrophil production of LTB4 is responsible for a second wave of neutrophil recruitment during inflammation, a process termed “swarming” (Lammermann et al, 2013). This is one of many examples of amplification loops initiated by neutrophils (Nemeth and Mocsai, 2016). …”

Section: Phenotypic Changes During Primingmentioning

confidence: 97%

Multiple Phenotypic Changes Define Neutrophil Priming

Miralda

Uriarte

McLeish

2017

Front. Cell. Infect. Microbiol.

143

176

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Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS) by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis. This review summarizes the breadth of phenotypic changes associated with priming and reviews current knowledge of the molecular mechanisms behind those changes. We conclude that the current definition of priming is too restrictive. Priming represents a combination of enhanced responsiveness and activated functions that regulate both adaptive and innate immune responses.

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“…Neutrophils have classically been considered to be prototypical short-lived and terminally differentiated phagocytes involved in innate immune responses following their rapid recruitment at site of infections and acute inflammation123. Compared to other leukocytes, their life span does not exceed 1–5 days in the circulation4 though several cytokines such as GM-CSF56, bacteria-derived products7, hypoxia8 or their migration through the blood vessel walls910 can significantly expand their life expectancy both in vivo and in vitro .…”

mentioning

confidence: 99%

Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation

Arokiasamy

Zakian

Dilliway

et al. 2017

Sci Rep

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Neutrophils are recognised to play a pivotal role at the interface between innate and acquired immunities following their recruitment to inflamed tissues and lymphoid organs. While neutrophil trafficking through blood vessels has been extensively studied, the molecular mechanisms regulating their migration into the lymphatic system are still poorly understood. Here, we have analysed neutrophil-lymphatic vessel interactions in real time and in vivo using intravital confocal microscopy applied to inflamed cremaster muscles. We show that antigen sensitisation of the tissues induces a rapid but transient entry of tissue-infiltrated neutrophils into lymphatic vessels and subsequent crawling along the luminal side of the lymphatic endothelium. Interestingly, using mice deficient in both TNF receptors p55 and p75, chimeric animals and anti-TNFα antibody blockade we demonstrate that tissue-release of TNFα governs both neutrophil migration through the lymphatic endothelium and luminal crawling. Mechanistically, we show that TNFα primes directly the neutrophils to enter the lymphatic vessels in a strictly CCR7-dependent manner; and induces ICAM-1 up-regulation on lymphatic vessels, allowing neutrophils to crawl along the lumen of the lymphatic endothelium in an ICAM-1/MAC-1-dependent manner. Collectively, our findings demonstrate a new role for TNFα as a key regulator of neutrophil trafficking into and within lymphatic system in vivo.

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Feedback Amplification of Neutrophil Function

Cited by 69 publications

References 109 publications

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

Multiple Phenotypic Changes Define Neutrophil Priming

Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation

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