Nucleosomes and neutrophil activation in sickle cell disease painful crisis
Marein Schimmel,
Erfan Nur,
Bart J. Biemond,
Gerard J. van Mierlo,
Shabnam Solati,
Dees P. Brandjes,
Hans-Martin Otten,
John-John Schnog,
Sacha Zeerleder
Affiliations
Marein Schimmel
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands;Department of Clinical Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Erfan Nur
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands;Department of Clinical Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Bart J. Biemond
Department of Clinical Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Gerard J. van Mierlo
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC, University of Amsterdam, Amsterdam, The Netherlands
Shabnam Solati
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC, University of Amsterdam, Amsterdam, The Netherlands
Dees P. Brandjes
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands
Hans-Martin Otten
Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands
John-John Schnog
Department of Hematology/Oncology, Saint Elisabeth Hospital, Willemstad, Curaçao;Department of Immunology, Red Cross Blood Bank Foundation, Willemstad, Curaçao
Sacha Zeerleder
Department of Clinical Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC, University of Amsterdam, Amsterdam, The Netherlands
Activated polymorphonuclear neutrophils play an important role in the pathogenesis of vaso-occlusive painful sickle cell crisis. Upon activation, polymorphonuclear neutrophils can form neutrophil extracellular traps. Neutrophil extracellular traps consist of a meshwork of extracellular DNA, nucleosomes, histones and neutrophil proteases. Neutrophil extracellular traps have been demonstrated to be toxic to endothelial and parenchymal cells. This prospective cohort study was conducted to determine neutrophil extracellular trap formation in sickle cell patients during steady state and painful crisis. As a measure of neutrophil extracellular traps, plasma nucleosomes levels were determined and polymorphonuclear neutrophil activation was assessed measuring plasma levels of elastase-α1-antitrypsin complexes in 74 patients in steady state, 70 patients during painful crisis, and 24 race-matched controls using Enzyme Linked Immunosorbent Assay. Nucleosome levels in steady state sickle cell patients were significantly higher than levels in controls. During painful crisis levels of both nucleosomes and elastase-α1-antitrypsin complexes increased significantly. Levels of nucleosomes correlated significantly to elastase-α1-antitrypsin complex levels during painful crisis, (Sr = 0.654, P
