Glycoxidated ferritin induces the release of microparticles positive for Toll-like receptors derived from peripheral blood CD14+ cells

Luis Fernando López Soto, Jose Manuel Galván Moroyoqui, Juan Manuel Martínez Soto, Martín Almada Balderrama, Ashley Patricia Rosales Ruíz, Gerardo Álvarez Hernández, Alma Yolanda Camacho Villa, Enrique Bolado Martínez, Jesús Adriana Soto Guzmán, Maria Del Carmen Candia Plata


Both increased serum ferritin levels and Toll-like receptor (TLR) activation show independent association with the inflammatory processes. During inflammation, cell activation and apoptosis are accompanied by the release of membrane-derived microparticles (MPs), which are considered to be mediators of intercellular communication as they induce specific responses in target cells. The aim of this study was to determine whether glycated and glycoxidated ferritin induce in vitro release TLR microparticles from CD14+ peripheral blood mononuclear cells. Peripheral blood mononuclear cells were stimulated with glycated, glycoxidated and native ferritin. The release of microparticles from CD14+ cells, the presence of TLR2+ and TLR4+ on the microparticles surface and the presence of interleukins-6 and -8 (IL-6 and IL-8) inside the microparticles after stimulation were determined by flow cytometry. The role of nuclear factor κB (NF-κB) was evaluated by pretreatment of the cells with the Bay 11-7085 inhibitor. Glycated and glycoxidated ferritin induced the release of microparticles from CD14+ cells, the majority of which expressed TLR2+ and TLR4+ on their surface and contained IL-6 and IL-8. These effects were dependent on NF-κB activation. Our findings show that glycated and glycoxidated ferritin might be involved in the release of microparticles and stimulation of inflammatory responses.

Received: June 14, 2016; Revised: August 20, 2016; Accepted: August 22, 2016; Published online: October 31, 2016

How to cite: López-Soto LF, Galván-Moroyoqui JM, Martínez-Soto JM, Almada-Balderrama M, Rosales-Ruiz AP, Álvarez-Hernández G, Camacho Villa AY, Bolado Martínez E, Soto-Guzmán JA, Candia-Plata MDC. Glycoxidated ferritin induces the release of microparticles positive for toll-like receptors derived from peripheral blood CD14+ cells. Arch Biol Sci. 2017;69(3):383-90.


microparticles; Toll-like receptor (TLR); ferritin; glycation; inflammation

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Ashourpour M, Djalali M, Djazayery A, Eshraghian MR, Taghdir M, Saedisomeolia A. Relationship between serum ferritin and inflammatory biomarkers with insulin resistance in a Persian population with type 2 diabetes and healthy people. Int J Food Sci Nutr. 2010;61(3):316-23.

Aso Y, Takebayashi K, Wakabayashi S, Momobayashi A, Sugawara N, Terasawa T, Naruse R, Hara K, Suetsugu M, Morita K, Inukai T. Relation between serum high molecular weight adiponectin and serum ferritin or prohepcidin in patients with type 2 diabetes. Diabetes Res Clin Pract. 2010;90(3):250-5.

Li J, Wang R, Luo D, Li S, Xiao C. Association between serum ferritin levels and risk of the metabolic syndrome in Chinese adults: a population study. PLoS One. 2013;8(9):e74168.

Williams MJ, Poulton R, Williams S. Relationship of serum ferritin with cardiovascular risk factors and inflammation in young men and women. Atherosclerosis. 2002;165(1):179-84.

Roseblade A, Luk F, Rawling T, Ung A, Grau GE, Bebawy M. Cell-derived microparticles: new targets in the therapeutic management of disease. J Pharm Pharm Sci. 2013;16(2):238-53.

Hodgkinson CP, Laxton RC, Patel K, Ye S. Advanced glycation end-product of low density lipoprotein activates the toll-like 4 receptor pathway implications for diabetic atherosclerosis. Arterioscler Thromb Vasc Biol. 2008;28(12):2275-81.

Hu H, Jiang H, Ren H, Hu X, Wang X, Han C. AGEs and chronic subclinical inflammation in diabetes: disorders of immune system. Diabetes Metab Res Rev. 2015;31(2):127-37.

Pang JH, Jiang MJ, Chen YL, Wang FW, Wang DL, Chu SH, Chau LY. Increased ferritin gene expression in atherosclerotic lesions. J Clin Invest. 1996;97(10):2204-12.

Galván-Moroyoqui JM C-PM, Martínez-Soto JM, Soto-Guzmán JA, Bolado Martínez E, Camacho-Villa AY, López-Soto LF. Glycated ferritin induces activation and expression of tlr2 and tlr4 in human peripheral blood macrophages. Pharma Innov J. 2015;3(12):44-8.

Hargett LA, Bauer NN. On the origin of microparticles: From "platelet dust" to mediators of intercellular communication. Pulm Circ. 2013;3(2):329-40.

Hoyer FF, Giesen MK, Nunes Franca C, Lutjohann D, Nickenig G, Werner N. Monocytic microparticles promote atherogenesis by modulating inflammatory cells in mice. J Cell Mol Med. 2012;16(11):2777-88.

Burger D, Thibodeau JF, Holterman CE, Burns KD, Touyz RM, Kennedy CR. Urinary podocyte microparticles identify prealbuminuric diabetic glomerular injury. J Am Soc Nephrol. 2014;25(7):1401-7.

Giannopoulos G, Oudatzis G, Paterakis G, Synetos A, Tampaki E, Bouras G, Hahalis G, Alexopoulos D, Tousoulis D, Cleman MW, Stefanadis C, Deftereos S. Red blood cell and platelet microparticles in myocardial infarction patients treated with primary angioplasty. Int J Cardiol. 2014;176(1):145-50.

Ikeda Y, Adachi Y, Ishibashi K, Miura N, Ohno N. Activation of toll-like receptor-mediated NF-kappa beta by zymosan-derived water-soluble fraction: possible contribution of endotoxin-like substances. Immunopharmacol Immunotoxicol. 2005;27(2):285-98.

Ravandi A, Kuksis A, Shaikh NA. Glucosylated glycerophosphoethanolamines are the major LDL glycation products and increase LDL susceptibility to oxidation: evidence of their presence in atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20(2):467-77.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.

Pierce JW, Schoenleber R, Jesmok G, Best J, Moore SA, Collins T, Gerritsen ME. Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J Biol Chem. 1997;272(34):21096-103.

Bessich JL, Nymon AB, Moulton LA, Dorman D, Ashare A. Low levels of insulin-like growth factor-1 contribute to alveolar macrophage dysfunction in cystic fibrosis. J Immunol. 2013;191(1):378-85.

Santos JM, Barcia RN, Simoes SI, Gaspar MM, Calado S, Agua-Doce A, Almeida SC, Almeida J, Filipe M, Teixeira M, Martins JP, Graca L, Cruz ME, Cruz P, Cruz H. The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX(R)) in the treatment of inflammatory arthritis. J Transl Med. 2013;11:18.

Jehn M, Clark JM, Guallar E. Serum ferritin and risk of the metabolic syndrome in U.S. adults. Diabetes Care. 2004;27(10):2422-8.

An SH, Lee MS, Kang JH. Oxidative modification of ferritin induced by methylglyoxal. BMB Rep. 2012;45(3):147-52.

Yoon JH, An SH, Kyeong IG, Lee MS, Kwon SC, Kang JH. Oxidative modification of ferritin induced by hydrogen peroxide. BMB Rep. 2011;44(3):165-9.

Miller YI, Chang MK, Binder CJ, Shaw PX, Witztum JL. Oxidized low density lipoprotein and innate immune receptors. Curr Opin Lipidol. 2003;14(5):437-45.

Nomura S, Shouzu A, Omoto S, Nishikawa M, Iwasaka T, Fukuhara S. Activated platelet and oxidized LDL induce endothelial membrane vesiculation: clinical significance of endothelial cell-derived microparticles in patients with type 2 diabetes. Clin Appl Thromb Hemost. 2004;10(3):205-15.

Angelillo-Scherrer A. Leukocyte-derived microparticles in vascular homeostasis. Circ Res. 2012;110(2):356-69.

Montoro-Garcia S, Shantsila E, Marin F, Blann A, Lip GY. Circulating microparticles: new insights into the biochemical basis of microparticle release and activity. Basic Res Cardiol. 2011;106(6):911-23.

Gauley J, Pisetsky DS. The release of microparticles by RAW 264.7 macrophage cells stimulated with TLR ligands. J Leukoc Biol. 2010;87(6):1115-23.

Spencer DM, Gauley J, Pisetsky DS. The properties of microparticles from RAW 264.7 macrophage cells undergoing in vitro activation or apoptosis. Innate Immun. 2014;20(3):239-48.

Angelot F, Seilles E, Biichle S, Berda Y, Gaugler B, Plumas J, Chaperot L, Dignat-George F, Tiberghien P, Saas P, Garnache-Ottou F. Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases. Haematologica. 2009;94(11):1502-12.

Distler JH, Huber LC, Gay S, Distler O, Pisetsky DS. Microparticles as mediators of cellular cross-talk in inflammatory disease. Autoimmunity. 2006;39(8):683-90.

Koppler B, Cohen C, Schlondorff D, Mack M. Differential mechanisms of microparticle transfer toB cells and monocytes: anti-inflammatory propertiesof microparticles. Eur J Immunol. 2006;36(3):648-60.


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