Impairment of neutrophil oxidative burst in children with sickle cell disease is associated with heme oxygenase-1

Haematologica
Ceri EvansAubrey J Cunnington

Abstract

Sickle cell disease is a risk factor for invasive bacterial infections, and splenic dysfunction is believed to be the main underlying cause. We have previously shown that the liberation of heme in acute hemolysis can induce heme oxygenase-1 during granulopoiesis, impairing the ability of developing neutrophils to mount a bactericidal oxidative burst, and increasing susceptibility to bacterial infection. We hypothesized that this may also occur with the chronic hemolysis of sickle cell disease, potentially contributing to susceptibility to infections. We found that neutrophil oxidative burst activity was significantly lower in treatment-naïve children with sickle cell disease compared to age-, gender- and ethnicity-matched controls, whilst degranulation was similar. The defect in neutrophil oxidative burst was quantitatively related to both systemic heme oxygenase-1 activity (assessed by carboxyhemoglobin concentration) and neutrophil mobilization. A distinct population of heme oxygenase-1-expressing cells was present in the bone marrow of children with sickle cell disease, but not in healthy children, with a surface marker profile consistent with neutrophil progenitors (CD49d(Hi) CD24(Lo) CD15(Int) CD16(Int) CD11b(+/-)). Incuba...Continue Reading

Citations

Feb 21, 2018·Current Opinion in Hematology·Hui Zhong, Karina Yazdanbakhsh
Nov 6, 2018·Current Opinion in Hematology·Katja L VogtAlison M Condliffe
Dec 21, 2018·Journal of Leukocyte Biology·Jason P MooneyEleanor M Riley
Mar 23, 2019·Pediatric Blood & Cancer·Hemant S Agarwal, John F Kuttesch
Jul 22, 2020·Human Vaccines & Immunotherapeutics·Giulia Piccini, Emanuele Montomoli
Nov 16, 2019·Scientific Reports·Laila ElsherifLeslie V Parise
May 22, 2020·Immunology Letters·Júlia Teixeira Cottas de Azevedo, Kelen Cristina Ribeiro Malmegrim

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