Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome
Abstract
:1. Introduction
2. Results
2.1. Platelets Did Not Contribute to Stx2-Mediated Damage to Human Glomerular Endothelial Cells (HGEC)
2.2. Stx2-Mediated Damage to HGEC Induced Platelet Adhesion
2.3. Stx2-Mediated HGEC Damage Induced Platelet to Release sCD40L
2.4. ROS Did Not Contribute to Stx2-Mediated Damage to HGEC or Platelet Adhesion
2.5. Oxidative Stress was Involved in the Platelet sCD40L Release
2.6. HUS Patients Had Increased Levels of sCD40L in Circulation
2.7. Plasma sCD40L Induced ROS Generation by Monocytes
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. HGEC Cultures
4.3. Human Platelets Isolation
4.4. HGEC-Platelets Cultures
4.5. NAC Treatment
4.6. Hematoxylin-Eosin (H&E) Staining
4.7. Neutral Red Cytotoxicity Assay
4.8. Acid Phosphatase Assay
4.9. Patients and Samples
4.10. sCD40L Measurement
4.11. Plasma Depletion of sCD40L
4.12. PBMC Isolation
4.13. ROS Generation Measurement
4.14. Data Analysis
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Palermo, M.S.; Exeni, R.A.; Fernandez, G.C. Hemolytic uremic syndrome: Pathogenesis and update of interventions. Expert Rev. Anti-Infect. Ther. 2009, 7, 697–707. [Google Scholar] [CrossRef] [PubMed]
- Schuller, S.; Frankel, G.; Phillips, A.D. Interaction of shiga toxin from Escherichia coli with human intestinal epithelial cell lines and explants: Stx2 induces epithelial damage in organ culture. Cell. Microbiol. 2004, 6, 289–301. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, A.D.; Tesh, V.L.; Donohue-Rolfe, A.; Jackson, M.P.; Olsnes, S.; Sandvig, K.; Lindberg, A.A.; Keusch, G.T. Shiga toxin: Biochemistry, genetics, mode of action, and role in pathogenesis. Curr. Top. Microbiol. Immunol. 1992, 180, 65–94. [Google Scholar] [PubMed]
- Gallo, E.G.; Gianantonio, C.A. Extrarenal involvement in diarrhoea-associated haemolytic-uraemic syndrome. Pediatr. Nephrol. 1995, 9, 117–119. [Google Scholar] [CrossRef] [PubMed]
- Ruggenenti, P.; Noris, M.; Remuzzi, G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int. 2001, 60, 831–846. [Google Scholar] [CrossRef] [PubMed]
- Morigi, M.; Galbusera, M.; Binda, E.; Imberti, B.; Gastoldi, S.; Remuzzi, A.; Zoja, C.; Remuzzi, G. Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood 2001, 98, 1828–1835. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moake, J.L. Thrombotic microangiopathies. N. Engl. J. Med. 2002, 347, 589–600. [Google Scholar] [CrossRef] [PubMed]
- Guessous, F.; Marcinkiewicz, M.; Polanowska-Grabowska, R.; Kongkhum, S.; Heatherly, D.; Obrig, T.; Gear, A.R. Shiga toxin 2 and lipopolysaccharide induce human microvascular endothelial cells to release chemokines and factors that stimulate platelet function. Infect. Immun. 2005, 73, 8306–8316. [Google Scholar] [CrossRef] [PubMed]
- Van Setten, P.A.; Monnens, L.A.; Verstraten, R.G.; van den Heuvel, L.P.; van Hinsbergh, V.W. Effects of verocytotoxin-1 on nonadherent human monocytes: Binding characteristics, protein synthesis, and induction of cytokine release. Blood 1996, 88, 174–183. [Google Scholar] [PubMed]
- Fong, J.S.; Kaplan, B.S. Impairment of platelet aggregation in hemolytic uremic syndrome: Evidence for platelet “exhaustion”. Blood 1982, 60, 564–570. [Google Scholar] [PubMed]
- Sassetti, B.; Vizcarguenaga, M.I.; Zanaro, N.L.; Silva, M.V.; Kordich, L.; Florentini, L.; Diaz, M.; Vitacco, M.; Sanchez Avalos, J.C. Hemolytic uremic syndrome in children: Platelet aggregation and membrane glycoproteins. J. Pediatr. Hematol. Oncol. 1999, 21, 123–128. [Google Scholar] [CrossRef] [PubMed]
- Von Hundelshausen, P.; Weber, C. Platelets as immune cells: Bridging inflammation and cardiovascular disease. Circ. Res. 2007, 100, 27–40. [Google Scholar] [CrossRef] [PubMed]
- Thomas, M.R.; Storey, R.F. The role of platelets in inflammation. Thromb. Haemost. 2015, 114, 449–458. [Google Scholar] [CrossRef] [PubMed]
- Blair, P.; Flaumenhaft, R. Platelet alpha-granules: Basic biology and clinical correlates. Blood Rev. 2009, 23, 177–189. [Google Scholar] [CrossRef] [PubMed]
- Schonbeck, U.; Libby, P. The CD40/CD154 receptor/ligand dyad. Cell. Mol. Life Sci. 2001, 58, 4–43. [Google Scholar] [PubMed]
- Van Kooten, C.; Banchereau, J. CD40-CD40 ligand. J. Leukoc. Biol. 2000, 67, 2–17. [Google Scholar] [PubMed]
- Freedman, J.E. CD40-CD40L and platelet function: Beyond hemostasis. Circ. Res. 2003, 92, 944–946. [Google Scholar] [CrossRef] [PubMed]
- Henn, V.; Slupsky, J.R.; Grafe, M.; Anagnostopoulos, I.; Forster, R.; Muller-Berghaus, G.; Kroczek, R.A. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998, 391, 591–594. [Google Scholar] [PubMed]
- Santilli, F.; Basili, S.; Ferroni, P.; Davi, G. CD40/CD40L system and vascular disease. Intern. Emerg. Med. 2007, 2, 256–268. [Google Scholar] [CrossRef] [PubMed]
- Ahn, E.R.; Lander, G.; Jy, W.; Bidot, C.J.; Jimenez, J.J.; Horstman, L.L.; Ahn, Y.S. Differences of soluble CD40L in sera and plasma: Implications on CD40L assay as a marker of thrombotic risk. Thromb. Res. 2004, 114, 143–148. [Google Scholar] [CrossRef] [PubMed]
- Andre, P.; Nannizzi-Alaimo, L.; Prasad, S.K.; Phillips, D.R. Platelet-derived CD40L: The switch-hitting player of cardiovascular disease. Circulation 2002, 106, 896–899. [Google Scholar] [CrossRef] [PubMed]
- Aloui, C.; Prigent, A.; Sut, C.; Tariket, S.; Hamzeh-Cognasse, H.; Pozzetto, B.; Richard, Y.; Cognasse, F.; Laradi, S.; Garraud, O. The signaling role of CD40 ligand in platelet biology and in platelet component transfusion. Int. J. Mol. Sci. 2014, 15, 22342–22364. [Google Scholar] [PubMed]
- Lutgens, E.; Daemen, M.J. CD40-CD40L interactions in atherosclerosis. Trends Cardiovasc. Med. 2002, 12, 27–32. [Google Scholar] [CrossRef]
- Urbich, C.; Dimmeler, S. CD40 and vascular inflammation. Can. J. Cardiol. 2004, 20, 681–683. [Google Scholar] [PubMed]
- Seijkens, T.; Kusters, P.; Engel, D.; Lutgens, E. CD40-CD40L: Linking pancreatic, adipose tissue and vascular inflammation in type 2 diabetes and its complications. Diabtes Vasc. Dis. Res. 2013, 10, 115–122. [Google Scholar] [CrossRef] [PubMed]
- Chakrabarti, S.; Blair, P.; Freedman, J.E. CD40-40L signaling in vascular inflammation. J. Biol. Chem. 2007, 282, 18307–18317. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.; Lee, W.H.; Lee, S.C.; Ahn, K.J.; Choi, Y.H.; Park, S.W.; Seo, J.D.; Park, J.E. CD40L activation in circulating platelets in patients with acute coronary syndrome. Cardiology 1999, 92, 11–16. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.P.; Ataga, K.I.; Orringer, E.P.; Phillips, D.R.; Parise, L.V. Biologically active CD40 ligand is elevated in sickle cell anemia: Potential role for platelet-mediated inflammation. Arterioscler. Thromb. Vasc. Biol. 2006, 26, 1626–1631. [Google Scholar] [CrossRef] [PubMed]
- Wiley, J.A.; Geha, R.; Harmsen, A.G. Exogenous CD40 ligand induces a pulmonary inflammation response. J. Immunol. 1997, 158, 2932–2938. [Google Scholar] [PubMed]
- Lievens, D.; Zernecke, A.; Seijkens, T.; Soehnlein, O.; Beckers, L.; Munnix, I.C.; Wijnands, E.; Goossens, P.; van Kruchten, R.; Thevissen, L.; et al. Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis. Blood 2010, 116, 4317–4327. [Google Scholar] [CrossRef] [PubMed]
- Cipollone, F.; Chiarelli, F.; Davi, G.; Ferri, C.; Desideri, G.; Fazia, M.; Iezzi, A.; Santilli, F.; Pini, B.; Cuccurullo, C.; et al. Enhanced soluble cd40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: Effect of improved metabolic control. Diabetologia 2005, 48, 1216–1224. [Google Scholar] [CrossRef] [PubMed]
- Rizvi, M.; Pathak, D.; Freedman, J.E.; Chakrabarti, S. CD40-CD40 ligand interactions in oxidative stress, inflammation and vascular disease. Trends Mol. Med. 2008, 14, 530–538. [Google Scholar] [CrossRef] [PubMed]
- Chakrabarti, S.; Varghese, S.; Vitseva, O.; Tanriverdi, K.; Freedman, J.E. CD40 ligand influences platelet release of reactive oxygen intermediates. Arterioscler. Thromb. Vasc. Biol. 2005, 25, 2428–2434. [Google Scholar] [CrossRef] [PubMed]
- Vanichakarn, P.; Blair, P.; Wu, C.; Freedman, J.E.; Chakrabarti, S. Neutrophil CD40 enhances platelet-mediated inflammation. Thromb. Res. 2008, 122, 346–358. [Google Scholar] [CrossRef] [PubMed]
- Gomez, S.A.; Abrey-Recalde, M.J.; Panek, C.A.; Ferrarotti, N.F.; Repetto, M.G.; Mejias, M.P.; Fernandez, G.C.; Vanzulli, S.; Isturiz, M.A.; Palermo, M.S. The oxidative stress induced in vivo by shiga toxin-2 contributes to the pathogenicity of haemolytic uraemic syndrome. Clin. Exp. Immunol. 2011, 173, 463–472. [Google Scholar] [CrossRef] [PubMed]
- Yoshimura, K.; Fujii, J.; Yutsudo, T.; Kikuchi, R.; Soejima, T.; Shirahata, S.; Yoshida, S. No direct effects of shiga toxin 1 and 2 on the aggregation of human platelets in vitro. Thromb. Haemost. 1998, 80, 529–530. [Google Scholar] [PubMed]
- Viisoreanu, D.; Polanowska-Grabowska, R.; Suttitanamongkol, S.; Obrig, T.G.; Gear, A.R. Human platelet aggregation is not altered by shiga toxins 1 or 2. Thromb. Res. 2000, 98, 403–410. [Google Scholar] [CrossRef]
- Thorpe, C.M.; Flaumenhaft, R.; Hurley, B.; Jacewicz, M.; Acheson, D.W.; Keusch, G.T. Shiga toxins do not directly stimulate alpha-granule secretion or enhance aggregation of human platelets. Acta Haematol. 1999, 102, 51–55. [Google Scholar] [CrossRef] [PubMed]
- Karpman, D.; Papadopoulou, D.; Nilsson, K.; Sjogren, A.C.; Mikaelsson, C.; Lethagen, S. Platelet activation by shiga toxin and circulatory factors as a pathogenetic mechanism in the hemolytic uremic syndrome. Blood 2001, 97, 3100–3108. [Google Scholar] [CrossRef] [PubMed]
- Ferraris, V.; Acquier, A.; Ferraris, J.R.; Vallejo, G.; Paz, C.; Mendez, C.F. Oxidative stress status during the acute phase of haemolytic uraemic syndrome. Nephrol. Dial. Transplant. 2010, 26, 858–864. [Google Scholar] [CrossRef] [PubMed]
- Li Volti, S.; Di Giacomo, C.; Garozzo, R.; Campisi, A.; Mollica, F.; Vanella, A. Impaired antioxidant defense mechanisms in two children with hemolytic-uremic syndrome. Ren. Fail. 1993, 15, 523–528. [Google Scholar] [CrossRef] [PubMed]
- Sahin, G.; Yalcin, A.U.; Akcar, N. Effect of N-acetylcysteine on endothelial dysfunction in dialysis patients. Blood Purif. 2007, 25, 309–315. [Google Scholar] [CrossRef] [PubMed]
- Gianantonio, C.A.; Vitacco, M.; Mendilaharzu, F.; Gallo, G.E.; Sojo, E.T. The hemolytic-uremic syndrome. Nephron 1973, 11, 174–192. [Google Scholar] [CrossRef] [PubMed]
- Kiener, P.A.; Moran-Davis, P.; Rankin, B.M.; Wahl, A.F.; Aruffo, A.; Hollenbaugh, D. Stimulation of CD40 with purified soluble gp39 induces proinflammatory responses in human monocytes. J. Immunol. 1995, 155, 4917–4925. [Google Scholar] [PubMed]
- Suttles, J.; Milhorn, D.M.; Miller, R.W.; Poe, J.C.; Wahl, L.M.; Stout, R.D. CD40 signaling of monocyte inflammatory cytokine synthesis through an ERK1/2-dependent pathway. A target of interleukin (IL)-4 and IL-10 anti-inflammatory action. J. Biol. Chem. 1999, 274, 5835–5842. [Google Scholar] [CrossRef] [PubMed]
- Granger, D.N.; Vowinkel, T.; Petnehazy, T. Modulation of the inflammatory response in cardiovascular disease. Hypertension 2004, 43, 924–931. [Google Scholar] [CrossRef] [PubMed]
- Harding, S.A.; Sarma, J.; Josephs, D.H.; Cruden, N.L.; Din, J.N.; Twomey, P.J.; Fox, K.A.; Newby, D.E. Upregulation of the CD40/CD40 ligand dyad and platelet-monocyte aggregation in cigarette smokers. Circulation 2004, 109, 1926–1929. [Google Scholar] [CrossRef] [PubMed]
- Libby, P. Multiple mechanisms of thrombosis complicating atherosclerotic plaques. Clin. Cardiol. 2000, 23 (Suppl. 6), 3–7. [Google Scholar] [CrossRef]
- Boerlin, P.; McEwen, S.A.; Boerlin-Petzold, F.; Wilson, J.B.; Johnson, R.P.; Gyles, C.L. Associations between virulence factors of shiga toxin-producing Escherichia coli and disease in humans. J. Clin. Microbiol. 1999, 37, 497–503. [Google Scholar] [PubMed]
- Ostroff, S.M.; Tarr, P.I.; Neill, M.A.; Lewis, J.H.; Hargrett-Bean, N.; Kobayashi, J.M. Toxin genotypes and plasmid profiles as determinants of systemic sequelae in Escherichia coli O157:H7 infections. J. Infect. Dis. 1989, 160, 994–998. [Google Scholar] [CrossRef] [PubMed]
- Bauwens, A.; Bielaszewska, M.; Kemper, B.; Langehanenberg, P.; von Bally, G.; Reichelt, R.; Mulac, D.; Humpf, H.U.; Friedrich, A.W.; Kim, K.S.; et al. Differential cytotoxic actions of shiga toxin 1 and shiga toxin 2 on microvascular and macrovascular endothelial cells. Thromb. Haemost. 2011, 105, 515–528. [Google Scholar] [CrossRef] [PubMed]
- Louise, C.B.; Obrig, T.G. Specific interaction of Escherichia coli o157:H7-derived shiga-like toxin ii with human renal endothelial cells. J. Infect. Dis. 1995, 172, 1397–1401. [Google Scholar] [CrossRef] [PubMed]
- Pignatelli, P.; Sanguigni, V.; Lenti, L.; Ferro, D.; Finocchi, A.; Rossi, P.; Violi, F. Gp91phox-dependent expression of platelet CD40 ligand. Circulation 2004, 110, 1326–1329. [Google Scholar] [CrossRef] [PubMed]
- Pignatelli, P.; Sanguigni, V.; Paola, S.G.; Lo Coco, E.; Lenti, L.; Violi, F. Vitamin c inhibits platelet expression of CD40 ligand. Free Radic. Biol. Med. 2005, 38, 1662–1666. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ruckerl, R.; Phipps, R.P.; Schneider, A.; Frampton, M.; Cyrys, J.; Oberdorster, G.; Wichmann, H.E.; Peters, A. Ultrafine particles and platelet activation in patients with coronary heart disease—Results from a prospective panel study. Part. Fibre Toxicol. 2007, 4, 1. [Google Scholar] [CrossRef] [PubMed]
- Garlichs, C.D.; John, S.; Schmeisser, A.; Eskafi, S.; Stumpf, C.; Karl, M.; Goppelt-Struebe, M.; Schmieder, R.; Daniel, W.G. Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia. Circulation 2001, 104, 2395–2400. [Google Scholar] [CrossRef] [PubMed]
- Yngen, M.; Ostenson, C.G.; Hu, H.; Li, N.; Hjemdahl, P.; Wallen, N.H. Enhanced p-selectin expression and increased soluble CD40 ligand in patients with type 1 diabetes mellitus and microangiopathy: Evidence for platelet hyperactivity and chronic inflammation. Diabetologia 2004, 47, 537–540. [Google Scholar] [CrossRef] [PubMed]
- Davidson, D.C.; Hirschman, M.P.; Sun, A.; Singh, M.V.; Kasischke, K.; Maggirwar, S.B. Excess soluble CD40L contributes to blood brain barrier permeability in vivo: Implications for hiv-associated neurocognitive disorders. PLoS ONE 2012, 7, e51793. [Google Scholar] [CrossRef] [PubMed]
- Sipsas, N.V.; Sfikakis, P.P.; Kontos, A.; Kordossis, T. Levels of soluble CD40 ligand (CD154) in serum are increased in human immunodeficiency virus type 1-infected patients and correlate with CD4(+) T-cell counts. Clin. Diagn. Lab. Immunol. 2002, 9, 558–561. [Google Scholar] [CrossRef] [PubMed]
- Ha, Y.J.; Lee, J.R. Role of TNF receptor-associated factor 3 in the CD40 signaling by production of reactive oxygen species through association with p40phox, a cytosolic subunit of nicotinamide adenine dinucleotide phosphate oxidase. J. Immunol. 2004, 172, 231–239. [Google Scholar] [CrossRef] [PubMed]
- Stahl, A.L.; Sartz, L.; Nelsson, A.; Bekassy, Z.D.; Karpman, D. Shiga toxin and lipopolysaccharide induce platelet-leukocyte aggregates and tissue factor release, a thrombotic mechanism in hemolytic uremic syndrome. PLoS ONE 2009, 4, e6990. [Google Scholar] [CrossRef] [PubMed]
- Sanguigni, V.; Ferro, D.; Pignatelli, P.; Del Ben, M.; Nadia, T.; Saliola, M.; Sorge, R.; Violi, F. CD40 ligand enhances monocyte tissue factor expression and thrombin generation via oxidative stress in patients with hypercholesterolemia. J. Am. Coll. Cardiol. 2005, 45, 35–42. [Google Scholar] [CrossRef] [PubMed]
- Shishehbor, M.H.; Hazen, S.L. Inflammatory and oxidative markers in atherosclerosis: Relationship to outcome. Curr. Atheroscler Rep. 2004, 6, 243–250. [Google Scholar] [CrossRef] [PubMed]
- Pignatelli, P.; Sanguigni, V.; Lenti, L.; Loffredo, L.; Carnevale, R.; Sorge, R.; Violi, F. Oxidative stress-mediated platelet CD40 ligand upregulation in patients with hypercholesterolemia: Effect of atorvastatin. J. Thromb. Haemost. 2007, 5, 1170–1178. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, G.; Sanders, J.M.; Bevard, M.H.; Sun, Z.; Chumley, J.W.; Galkina, E.V.; Ley, K.; Sarembock, I.J. CD40 ligand promotes Mac-1 expression, leukocyte recruitment, and neointima formation after vascular injury. Am. J. Pathol. 2008, 172, 1141–1152. [Google Scholar] [CrossRef] [PubMed]
- Jin, R.; Yu, S.; Song, Z.; Zhu, X.; Wang, C.; Yan, J.; Wu, F.; Nanda, A.; Granger, D.N.; Li, G. Soluble CD40 ligand stimulates CD40-dependent activation of the β 2 integrin Mac-1 and protein kinase C zeda (pkczeta) in neutrophils: Implications for neutrophil-platelet interactions and neutrophil oxidative burst. PLoS ONE 2013, 8, e64631. [Google Scholar]
- Bentancor, L.V.; Bilen, M.; Brando, R.J.; Ramos, M.V.; Ferreira, L.C.; Ghiringhelli, P.D.; Palermo, M.S. A DNA vaccine encoding the enterohemorragic Escherichia coli shiga-like toxin 2 A2 and B subunits confers protective immunity to shiga toxin challenge in the murine model. Clin. Vaccine Immunol. 2009, 16, 712–718. [Google Scholar] [CrossRef] [PubMed]
- Amaral, M.M.; Sacerdoti, F.; Jancic, C.; Repetto, H.A.; Paton, A.W.; Paton, J.C.; Ibarra, C. Action of shiga toxin type-2 and subtilase cytotoxin on human microvascular endothelial cells. PLoS ONE 2013, 8, e70431. [Google Scholar] [CrossRef] [PubMed]
- Fischer, A.H.; Jacobson, K.A.; Rose, J.; Zeller, R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. 2008, 2008. [Google Scholar] [CrossRef] [PubMed]
- Creydt, V.P.; Silberstein, C.; Zotta, E.; Ibarra, C. Cytotoxic effect of shiga toxin-2 holotoxin and its b subunit on human renal tubular epithelial cells. Microbes Infect. 2006, 8, 410–419. [Google Scholar] [CrossRef] [PubMed]
- Etulain, J.; Negrotto, S.; Carestia, A.; Pozner, R.G.; Romaniuk, M.A.; D’Atri, L.P.; Klement, G.L.; Schattner, M. Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets. Thromb. Haemost. 2012, 107, 99–110. [Google Scholar] [CrossRef] [PubMed]
- Zhang, P.; Zhong, L.; Struble, E.B.; Watanabe, H.; Kachko, A.; Mihalik, K.; Virata-Theimer, M.L.; Alter, H.J.; Feinstone, S.; Major, M. Depletion of interfering antibodies in chronic hepatitis c patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity. Proc. Natl. Acad. Sci. USA 2009, 106, 7537–7541. [Google Scholar] [CrossRef] [PubMed]
- Boyum, A. Separation of leukocytes from blood and bone marrow. Introduction. Scand. J. Clin. Lab. Investig. Suppl. 1968, 97, 7. [Google Scholar]
Severity of Renal Dysfunction | ||
General Parameters | Grade 1 y 2 (n = 13) | Grade 3 (n = 10) |
Age (month) | 45.0 (22.0–81.2) | 21.5 (10.5–60.5) |
Time from the onset of diarrhea (days) a | 4.0 (3.0–5.0) | 4.5(1.7–9.7) |
Blood and Renal Parameters | ||
Platelets (×109/L) | 77.5 (39.2–34.5) | 45.0 (34.5–57.0) |
Leukocytes (×109/L) | 14.0 (8.9–22.3) | 17.4 (13.8–31.0) |
Hematocrit (%) | 24.0 (19.3–26.0) | 24.2 (23.0–25.7) |
Urea (mmol/L) | 15.6 (10.5–25.9) | 39.7 (26.6–54.3) |
Creatinine (µmol/L) | 110.5 (61.8–223.2) | 419.9 (235.4–795.6) |
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Abrey Recalde, M.J.; Alvarez, R.S.; Alberto, F.; Mejias, M.P.; Ramos, M.V.; Fernandez Brando, R.J.; Bruballa, A.C.; Exeni, R.A.; Alconcher, L.; Ibarra, C.A.; et al. Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome. Toxins 2017, 9, 331. https://doi.org/10.3390/toxins9110331
Abrey Recalde MJ, Alvarez RS, Alberto F, Mejias MP, Ramos MV, Fernandez Brando RJ, Bruballa AC, Exeni RA, Alconcher L, Ibarra CA, et al. Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome. Toxins. 2017; 9(11):331. https://doi.org/10.3390/toxins9110331
Chicago/Turabian StyleAbrey Recalde, Maria J., Romina S. Alvarez, Fabiana Alberto, Maria P. Mejias, Maria V. Ramos, Romina J. Fernandez Brando, Andrea C. Bruballa, Ramon A. Exeni, Laura Alconcher, Cristina A. Ibarra, and et al. 2017. "Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome" Toxins 9, no. 11: 331. https://doi.org/10.3390/toxins9110331