Binding, Trafficking and Accumulation of Serum Amyloid A in Peritoneal Macrophages

Kluve‐Beckerman, Barbara; Manaloor, John J.; Liepnieks, Juris J.

doi:10.1046/j.1365-3083.2001.00879.x

Cited by 39 publications

(41 citation statements)

References 22 publications

(26 reference statements)

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“…It is possible that once liberated from HDL, SAA undergoes structural changes or becomes susceptible to limited proteolysis and the modified protein triggers inflammasome activation. Our study, consistent with other reports (68,69) indicates that HDL does not prevent cellular uptake of SAA ( Fig.7G and H). According to one report, HDL-SAA is internalized through a clathrin-dependent endocytic pathway and then trafficked to lysosomes where it accumulates as SAA aggregates or amyloid deposits (69).…”

Section: Discussionsupporting

confidence: 94%

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High-density lipoprotein inhibits serum amyloid A–mediated reactive oxygen species generation and NLRP3 inflammasome activation

Shridas

Beer

Webb

2018

Journal of Biological Chemistry

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Serum amyloid A (SAA) is a high-density apolipoprotein whose plasma levels can increase more than 1000-fold during a severe acute-phase inflammatory response and are more modestly elevated in chronic inflammation. SAA is thought to play important roles in innate immunity, but its biological activities have not been completely delineated. We previously reported that SAA deficiency protects mice from developing abdominal aortic aneurysms (AAAs) induced by chronic angiotensin II (AngII) infusion. Here, we report that SAA is required for AngII-induced increases in interleukin-1 beta (IL-1β), a potent proinflammatory cytokine that is tightly controlled by the Nod-like receptor protein 3 (NLRP3) inflammasome and caspase-1 and has been implicated in both human and mouse AAAs. We determined that purified SAA stimulates IL-1β secretion in murine J774 and bone marrow-derived macrophages through a mechanism that depends on NLRP3 expression and caspase-1 activity, but is independent of P2X7 nucleotide receptor (P2X7R) activation. Inhibiting reactive oxygen species (ROS) by N-acetyl-Lcysteine or mito-TEMPO and inhibiting activation of cathepsin B by CA-074 blocked SAA-mediated inflammasome activation and IL-1β secretion. Moreover, inhibiting cellular potassium efflux with glyburide or increasing extracellular potassium also significantly reduced SAA-mediated IL-1β secretion. Of note, incorporating SAA into high-density lipid (HDL) prior to its use in cell treatments completely http://www.jbc.org/cgi

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Section: Discussionsupporting

confidence: 94%

“…Amyloid fibrils can cause disruption of lysosomal membranes (69), which may trigger inflammasome activation. However it seems unlikely that SAA fibril formation is responsible for triggering inflammasome activation in our study, as HDLbound SAA is capable of forming intracellular fibrils (68,69).…”

Section: Discussionmentioning

confidence: 64%

High-density lipoprotein inhibits serum amyloid A–mediated reactive oxygen species generation and NLRP3 inflammasome activation

Shridas

Beer

Webb

2018

Journal of Biological Chemistry

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“…Available data about the phagocytic activity and oxidative burst of PMN and monocytes during FMF are very contradictory. Some reports support the decrease in the phagocytic activity of PMN and monocytes [39,40] , while there are no notable changes in others [41,42] , and in studies regarding the mechanism of amyloidogenesis, in contrast, the activation of phagocytosis of monocytes/macrophages is noted as an important pathogenetic link [43] . In addition, a number of subtle abnormalities in PMN function, including enhanced chemiluminescence [44] , chemotaxis [45] , superoxide production [46] and lysozyme leak [40] , have been noted in patients with FMF.…”

Section: Discussionmentioning

confidence: 94%

Impaired Endotoxin Tolerance Induction in Patients with Familial Mediterranean Fever

Davtyan

Hakopyan²,

Avetisyan

et al. 2006

Pathobiology

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Objective: To investigate periodic disturbances in proinflammatory activation of neutrophils and monocytes in patients with familial Mediterranean fever (FMF) both during an attack and in remission. Methods: 20 FMF patients, who were naive to colchicine treatment and did not have amyloidosis, and 10 patients with Behçet’s disease (BD) were enrolled in this study. Phagocytosis, respiratory burst, CD11a/CD18 expression and intracellular cytokine synthesis were determined by flow cytometry. Endotoxin tolerance induction was defined by a reduced capacity of monocytes to respond to lipopolysaccharide (LPS) activation following a first exposure to LPS. Results:In FMF patients, we observed upregulation of neutrophil and monocyte phagocytic activity and oxidative burst during remission and downregulation of phagocytic activity and stimulus-dependent oxidative burst during an attack. A comparative analysis of oxidative burst has revealed that while the neutrophil population shows a certain periodicity in the increase (during remission) and decrease (during attacks) in the spontaneous and inducible respiratory burst, periodicity in the monocyte population is very poor. In addition, LPS-induced oxidative burst and CD11a/CD18 integrin surface expression is higher in patients during an attack compared to patients in remission. The induction of homologous tolerance of monocytes to the repeated action of LPS is observed in FMF patients during an attack, normal donors and patients with BD, whereas monocytes from patients in remission failed to induce LPS homologous tolerance and exhibited heightened sensitivity to bacterial endotoxin. We found that colchicine is able to restore impaired LPS homologous tolerance induction in FMF patients in remission upon increased synthesis of IL-4 in FMF patient monocytes. Conclusion: Chronic inflammation during FMF is characterized by periodic changes in monocyte and neutrophil activation and heightened sensitivity to endotoxin, which is associated with the episodic nature of FMF. Increased endotoxin sensitivity in the period of remission could result from a shift in the monocyte activation program from ‘alternatively’ into ‘classically’ activated monocytes, which may have important implications for the treatment of FMF.

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“…3A), which strongly argues against extracellular SAA fibril formation and phagocytosis-induced inflammasome activation. However, it has been reported that cytochalasin D-independent uptake of SAA by macrophages and subsequent formation of intracellular amyloid fibrils can take place when high SAA concentrations (.100 mg/ml) are used (49). Therefore, we studied whether SAA could induce lysosomal destabilization and leakage of cathepsin B into cytoplasm.…”

Section: Saa-induced Inflammasome Activation Is Dependent On Cathepsin Bmentioning

confidence: 99%

Serum Amyloid A Activates the NLRP3 Inflammasome via P2X7 Receptor and a Cathepsin B-Sensitive Pathway

Niemi

Teirilä

Lappalainen

et al. 2011

The Journal of Immunology

249

225

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Serum amyloid A (SAA) is an acute-phase protein, the serum levels of which can increase up to 1000-fold during inflammation. SAA has a pathogenic role in amyloid A-type amyloidosis, and increased serum levels of SAA correlate with the risk for cardiovascular diseases. IL-1β is a key proinflammatory cytokine, and its secretion is strictly controlled by the inflammasomes. We studied the role of SAA in the regulation of IL-1β production and activation of the inflammasome cascade in human and mouse macrophages, as well as in THP-1 cells. SAA could provide a signal for the induction of pro–IL-1β expression and for inflammasome activation, resulting in secretion of mature IL-1β. Blocking TLR2 and TLR4 attenuated SAA-induced expression of IL1B, whereas inhibition of caspase-1 and the ATP receptor P2X7 abrogated the release of mature IL-1β. NLRP3 inflammasome consists of the NLRP3 receptor and the adaptor protein apoptosis-associated speck-like protein containing CARD (a caspase-recruitment domain) (ASC). SAA-mediated IL-1β secretion was markedly reduced in ASC−/− macrophages, and silencing NLRP3 decreased IL-1β secretion, confirming NLRP3 as the SAA-responsive inflammasome. Inflammasome activation was dependent on cathepsin B activity, but it was not associated with lysosomal destabilization. SAA also induced secretion of cathepsin B and ASC. In conclusion, SAA can induce the expression of pro–IL-1β and activation of the NLRP3 inflammasome via P2X7 receptor and a cathepsin B-sensitive pathway. Thus, during systemic inflammation, SAA may promote the production of IL-1β in tissues. Furthermore, the SAA-induced secretion of active cathepsin B may lead to extracellular processing of SAA and, thus, potentially to the development of amyloid A amyloidosis.

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Binding, Trafficking and Accumulation of Serum Amyloid A in Peritoneal Macrophages

Cited by 39 publications

References 22 publications

High-density lipoprotein inhibits serum amyloid A–mediated reactive oxygen species generation and NLRP3 inflammasome activation

High-density lipoprotein inhibits serum amyloid A–mediated reactive oxygen species generation and NLRP3 inflammasome activation

Impaired Endotoxin Tolerance Induction in Patients with Familial Mediterranean Fever

Serum Amyloid A Activates the NLRP3 Inflammasome via P2X7 Receptor and a Cathepsin B-Sensitive Pathway

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