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.135102

Cited by 6 publications

(21 citation statements)

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“…Macrophages can clear pathogens, tissue debris, and necrotic and apoptotic cells through phagocytosis, and thus, play an important role in AP, since tissue injuries induced by NETs are caused by cell debris and thrombus formation. Organ failure in the late stage is caused by long-term continuous neutrophil-derived inflammation and endothelial injury [27,28]. These processes are paralleled by a pronounced immune reaction that amplifies disease severity, such as system inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS).…”

Section: Discussionmentioning

confidence: 99%

Roles of polymorph nuclear neutrophil elastase and thrombomodulin in patients with acute pancreatitis in the context of neutrophil extracellular traps

Fukuzawa¹,

Matuyama²,

Gotoh³

et al. 2022

World J. Bio. Pharm. Health Sci.

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The goal of the study was to evaluate progression of acute pancreatitis (AP) based on measurement of plasma levels of polymorph nuclear neutrophil (PMN) elastase, thrombomodulin (TM), lipopolysaccharide (LPS), thrombin-antithrombin III complex (TAT), and platelet counts associated with neutrophil extracellular trap (NETs). The subjects were 42 patients with AP, including 30 classified with mild AP (MAP) and 12 with severe AP (SAP), and 20 normal adult controls. Plasma levels of TM, PMN elastase, LPS, and TAT were measured by ELISA. Platelets were measured by a routine method. TM molecular subspecies were isolated from plasma using beads and analyzed by reverse-phase HPLC. After these measurements, ulinastatin was administered to 16 patients. TM, PMN elastase, LPS, and TAT levels in patients with AP were significantly higher than those in controls. Furthermore, these four markers were significantly higher in SAP cases than in MAP cases. Platelet counts significantly decreased in the order of SAP, MAP, and controls. Eight TM subspecies were present in plasma and most of these increased with aggravation of AP. The areas under the ROC curves for PMN elastase, TM, LPS, and TAT were 0.814, 0.827, 0.766, and 0.860, respectively. The markers were normalized by ulinastatin treatment in 16 patients with AP. At onset of focal AP, PMN elastase accumulates in platelets and leukocytes in NETs, and is released from neutrophils. This then releases TM from blood vessel walls, which activates coagulation and leads to systemic aggregation. Treatment with ulinastatin is effective for this disorder.

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Section: Discussionmentioning

confidence: 99%

Roles of polymorph nuclear neutrophil elastase and thrombomodulin in patients with acute pancreatitis in the context of neutrophil extracellular traps

Fukuzawa¹,

Matuyama²,

Gotoh³

et al. 2022

World J. Bio. Pharm. Health Sci.

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“…Активовані нейтрофіли виділяють мікрочастинки (МЧ), тобто сфероподібні інтактні везикули, що вивільняються з клітинних мембран розміром менше ніж 1 мкм [57], однак невідомо, чи МЧ зв'язані з НПП і сприяють запаленню та пошкодженню тканин при ГП [58]. Нещодавно було продемонстровано, що MЧ, що утворюються під час активації нейтрофілів, можуть зв'язуватися з НПП і формувати комплекси НПП-MЧ, які важливі для продукування тромбіну при сепсисі [59].…”

Section: мікрочастинки нейтрофілів і нпп при гпunclassified

Neutrophil Extracellular Traps in Acute Pancreatitis

Chooklin¹,

Chuklin²,

Barylyak³

2022

Fiziol Zh

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The review focuses on the role of neutrophilic extracellular traps (NETs) in the pathogenesis of acute pancreatitis. It is shown that NETs can activate trypsin, cause inflammation and pancreatic tissue damage, and clog the excretory ducts. NETs are involved in the formation of gallstones, which are one of the leading etiological factors of acute pancreatitis. NETs also surround necrotic tissue in patients with severe acute pancreatitis and contribute to further systemic inflammatory response syndrome. The mechanisms of NETs formation in acute pancreatitis, in particular, the importance of damageassociated molecular patterns, neutrophil microparticles, and platelets in these processes are considered.

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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][34][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: Neutrophils and Inflammationmentioning

confidence: 99%

“…A substantial number of studies have suggested that neutrophils are involved in the pathogenesis of AP [25,27,28,39,40, (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: Neutrophils Infiltration In the Pathogenesis Of Ap And Therapymentioning

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 6 publications

References 0 publications

Roles of polymorph nuclear neutrophil elastase and thrombomodulin in patients with acute pancreatitis in the context of neutrophil extracellular traps

Roles of polymorph nuclear neutrophil elastase and thrombomodulin in patients with acute pancreatitis in the context of neutrophil extracellular traps

Neutrophil Extracellular Traps in Acute Pancreatitis

The Role of Pancreatic Infiltrating Innate Immune Cells in Acute Pancreatitis

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