Platelet IP6K1 regulates neutrophil extracellular trap-microparticle complex formation in acute pancreatitis

Madhi, Raed; Rahman, Milladur; Taha, Dler; Linders, Johan; Merza, Mohammed; Wang, Yongzhi; Mörgelon, Matthias; Thorlacius, Henrik

doi:10.1172/jci.insight.129270

Cited by 11 publications

(14 citation statements)

References 40 publications

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“…Acute pancreatitis can be accompanied by severe systemic inflammation, hence there are immunological traits related to sepsis. A recent study showed that PMN-EVs associated with neutrophil extracellular traps in an animal model of acute pancreatitis contribute to both local and systemic deterioration of inflammation [ 135 ].…”

Section: Neutrophil-derived Evsmentioning

confidence: 99%

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

Kolonics

Szeifert

Tímár

et al. 2020

Cells

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Similar to other cell types, neutrophilic granulocytes also release extracellular vesicles (EVs), mainly medium-sized microvesicles/microparticles. According to published data, authors have reached a consensus on the physical parameters (size, density) and chemical composition (surface proteins, proteomics) of neutrophil-derived EVs. In contrast, there is large diversity and even controversy in the reported functional properties. Part of the discrepancy may be ascribed to differences in the viability of the starting cells, in eliciting factors, in separation techniques and in storage conditions. However, the most recent data from our laboratory prove that the same population of neutrophils is able to generate EVs with different functional properties, transmitting pro-inflammatory or anti-inflammatory effects on neighboring cells. Previously we have shown that Mac-1 integrin is a key factor that switches anti-inflammatory EV generation into pro-inflammatory and antibacterial EV production. This paper reviews current knowledge on the functional alterations initiated by neutrophil-derived EVs, listing their effects according to the triggering agents and target cells. We summarize the presence of neutrophil-derived EVs in pathological processes and their perspectives in diagnostics and therapy. Finally, the functional heterogeneity of differently triggered EVs indicates that neutrophils are capable of producing a broad spectrum of EVs, depending on the environmental conditions prevailing at the time of EV genesis.

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Section: Neutrophil-derived Evsmentioning

confidence: 99%

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

Kolonics

Szeifert

Tímár

et al. 2020

Cells

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“…Thrombin stimulation of IP6K1-deficient platelets in the presence of neutrophils results in no NET formation. NET formation induced by taurocholate reduced pancreatic inflammation and tissue damage in IP6K1-deficient mice (Madhi et al, 2019 ). Therefore, NETs play a role in mediating inflammation and thrombosis, bridging the transition between hypercoagulability and severe inflammation in the early pathophysiology of pancreatitis.…”

Section: The Proteins In Neutrophil Granules In Acute Pancreatitismentioning

confidence: 99%

The Role of Neutrophils and Neutrophil Extracellular Traps in Acute Pancreatitis

Wan

Ren

Yang

et al. 2021

Front. Cell Dev. Biol.

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Leukocyte invasion (neutrophils and monocytes/macrophages) is closely related to the severity of acute pancreatitis (AP) and plays an important role in the systemic inflammatory response and other organ injuries secondary to AP. Increased and sustained activation of neutrophils are major determinants of pancreatic injury and inflammation. After the onset of AP, the arrival of the first wave of neutrophils occurs due to a variety of triggers and is critical for the exacerbation of inflammation. In this review, we summarize the functional characteristics of neutrophils, elastase, and heparin-binding proteins in granules, the mechanisms of neutrophil recruitment and the role of neutrophil extracellular traps (NETs) in AP.

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“…NETs were initially thought to be a mechanism by which neutrophils clear pathogens, for example, the replication of staphylococcus aureus, salmonella typhimurium, streptococcus pneumoniae, and shigella flexneri can be inhibited by NETs 30 , 33 - 35 . But its critical role in sterile inflammation has also been revealed in recent years, such as deep venous thrombosis 36 , lung cancer 37 , arthritis 38 , AP 25 , 39 , 40 , endogenous particulate-related injury 41 , glioma 31 , liver ischemia-reperfusion injury 42 , ischemic stroke 43 , etc.…”

Section: Neutrophilsmentioning

confidence: 99%

“…A substantial number of studies have suggested that neutrophils are involved in the pathogenesis of AP 25 , 27 , 28 , 39 , 40 , 47 - 76 ( Figure 2 ). Measurements of MPO levels in serum 27 or pancreatic tissue 49 , 54 , 61 can reflect the number and activity of infiltrating neutrophils.…”

Section: Neutrophilsmentioning

confidence: 99%

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The Role of Pancreatic Infiltrating Innate Immune Cells in Acute Pancreatitis

Pan¹,

Li²,

Yu³

2021

Int. J. Med. Sci.

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Acute pancreatitis (AP) is a leading cause of gastrointestinal-related hospital admissions with significant morbidity and mortality. Although the underlying pathophysiology of AP is rather complex, which greatly limits the treatment options, more and more studies have revealed that infiltrating immune cells play a critical role in the pathogenesis of AP and determine disease severity. Thus, immunomodulatory therapy targeting immune cells and related inflammatory mediators is expected to be a novel treatment modality for AP which may improve the prognosis of patients. Cells of the innate immune system, including macrophages, neutrophils, dendritic cells, and mast cells, represent the majority of infiltrating cells during AP. In this review, an overview of different populations of innate immune cells and their role during AP will be discussed, with a special focus on neutrophils and macrophages.

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Platelet IP6K1 regulates neutrophil extracellular trap-microparticle complex formation in acute pancreatitis

Cited by 11 publications

References 40 publications

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

The Role of Neutrophils and Neutrophil Extracellular Traps in Acute Pancreatitis

The Role of Pancreatic Infiltrating Innate Immune Cells in Acute Pancreatitis

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