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

Evans, Ceri; Orf, Katharine; Horvath, Erzsebet; Levin, Michael; Fuente, Josu de la; Chakravorty, Subarna; Cunnington, Aubrey J.

doi:10.3324/haematol.2015.128777

Cited by 27 publications

(21 citation statements)

References 55 publications

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“…in mice via carbon monoxide production [18,38]. In humans, HO-1 induced by hemolysis, either from malaria [39] or sickle cell disease [40], can impair neutrophil function, leading to increased host susceptibility to bacterial infection. However, a direct role for HO-1 in malaria pathogenesis is less clear.…”

Section: Discussionmentioning

confidence: 99%

Whole-Blood Transcriptional Signatures Composed of Erythropoietic and NRF2-Regulated Genes Differ Between Cerebral Malaria and Severe Malarial Anemia

Nallandhighal

Park

et al. 2018

The Journal of Infectious Diseases

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Section: Discussionmentioning

confidence: 99%

Whole-Blood Transcriptional Signatures Composed of Erythropoietic and NRF2-Regulated Genes Differ Between Cerebral Malaria and Severe Malarial Anemia

Nallandhighal

Park

et al. 2018

The Journal of Infectious Diseases

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“…Nevertheless, neutrophil function is markedly diminished due to premature release of immature neutrophils from bone marrow 52 ; these immature cells migrate sub-optimally in response to cytokines and nitric oxide and have reduced capacity to produce reactive oxygen species (impaired oxidative burst) 53 – 55 . This release of defective neutrophils from bone marrow is mediated in large part by the HO-1 pathway 19 , 56 . Although the underlying defect in neutrophil maturation has not been characterized in sepsis, we speculate that HO-1 (or the products of HO-1 enzymatic activity) may impact innate immunity.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Anaemia, Haemolysis, Inflammation and Haem Oxygenase-1 at Admission with Sepsis: a pilot study

Ekregbesi

Shankar-Hari

Bottomley

et al. 2018

Sci Rep

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Upregulation of haem oxygenase-1 (HO-1), due to haemolysis and/or inflammation, can lead to impaired immune function. Anaemia is common among sepsis patients, but the consequences of sepsis-associated anaemia are poorly understood. Here, our objective was to determine the prevalence and extent of anaemia, haemolysis, inflammation, and HO-1 induction after early hospital admission. We hypothesised that inflammation- or infection-induced haemolysis contributes to sepsis-associated anaemia and that this will lead to expression of HO-1. In this study, plasma obtained from seventy adult patients within 12 hours of admission to intensive care due to sepsis were analysed for anaemia, haemolysis and inflammatory markers by ELISA and microbead array. The majority (82.6%) of patients were anaemic with evidence of haemolysis (raised haem, haptoglobin, haemopexin, and HO-1 concentrations). Interestingly, concentrations of both haemoglobin and IL-10 were moderately positively correlated with HO-1 concentration (Hb: r = 0.32, p = 0.007; IL-10 r = 0.39, p = 0.0008) whereas HO-1 concentration was weakly negatively correlated with haemopexin (r = −0.23, p = 0.055). Anaemia, while common, was not associated with HO-1 concentration. After adjusting for confounding, HO-1 induction appears to be associated primarily with IL-10 concentration rather than haemolysis. Disease severity at diagnosis was correlated with early plasma IL-10 (r = 0.35, p = 0.003) and HO-1 (r = 0.24, p = 0.048) concentrations. Notably, admission levels of haem, HO-1, and IL-10 were indicators of survival.

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“…Moreover, hmox1 induction increases NTS growth in murine macrophages, indicating that hemolysis (via heme and HO‐1) rather than malaria, per se, may be the true risk factor for invasive NTS disease in malaria patients. In support of this notion, individuals with sickle cell anemia, which gives rise to periodic hemolytic crises, are also highly susceptible to invasive NTS disease; similarly, induction of acute hemolysis by antibody‐mediated RBC lysis or phenylhydrazine treatment also renders mice highly susceptible to NTS.…”

Section: Hemolysis Heme Oxygenase‐1 and Neutrophil Function During mentioning

confidence: 93%

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Mooney

Galloway

Riley

2018

Journal of Leukocyte Biology

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Invasive bacterial disease is well described in immunocompromised hosts, including those with malaria infection. One bacterial infection frequently observed in children with Plasmodium falciparum infection is nontyphoidal salmonella (NTS) infection, in which a typically intestinal infection becomes systemic with serious, often fatal, consequences. In this review, we consider the role of malaria‐induced immunoregulatory responses in tipping the balance from tissue homeostasis during malaria infection to risk of invasive NTS. Also, neutrophils are crucial in the clearance of NTS but their ability to mount an oxidative burst and kill intracellular Salmonella is severely compromised during, and for some time after, an acute malaria infection. Here, we summarize the evidence linking malaria and invasive NTS infections; describe the role of neutrophils in clearing NTS infections; review evidence for neutrophil dysfunction in malaria infections; and explore roles of heme oxygenase‐1, IL‐10, and complement in mediating this dysfunction. Finally, given the epidemiological evidence that low density, subclinical malaria infections pose a risk for invasive NTS infections, we consider whether the high prevalence of such infections might underlie the very high incidence of invasive bacterial disease across much of sub‐Saharan Africa.

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

Cited by 27 publications

References 55 publications

Whole-Blood Transcriptional Signatures Composed of Erythropoietic and NRF2-Regulated Genes Differ Between Cerebral Malaria and Severe Malarial Anemia

Whole-Blood Transcriptional Signatures Composed of Erythropoietic and NRF2-Regulated Genes Differ Between Cerebral Malaria and Severe Malarial Anemia

Relationship between Anaemia, Haemolysis, Inflammation and Haem Oxygenase-1 at Admission with Sepsis: a pilot study

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

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