Emerging role of apoptosis in the pathogenesis of severe neutropenia

Aa, Aprikyan; Wc, Liles; Dale, DC

doi:10.1097/00062752-200005000-00001

Cited by 12 publications

(7 citation statements)

References 9 publications

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“…We now hypothesize that these mutations lead to accelerated apoptosis of developing neutrophil precursors. 33 Impaired survival observed in CN may be due to conformational changes in protein structure that result in aberrant subcellular localization or alterations in substrate specificity and/or binding properties of neutrophil elastase. Further investigations are in progress to characterize the molecular mechanism(s) underlying the pathogenesis of CN.…”

Section: R E T R a C T E D O N J U L Y 3 2 0 1mentioning

confidence: 99%

Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia

Aprikyan

Liles

Rodger

et al. 2001

Blood

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Cyclic neutropenia (CN) is a congenital hematopoietic disorder characterized by remarkably regular oscillations of blood neutrophils from near normal to extremely low levels at 21-day intervals. Recurring episodes of severe neutropenia lead to repetitive and sometimes life-threatening infections. To investigate the cellular mechanism of CN, the ultrastructure and the proliferative and survival characteristics of bone marrow-derived CD34(+) early progenitors, CD33(+)/CD34(-) myeloid progenitors, and CD15(+) neutrophil precursors from CN patients and healthy volunteers were studied. The ultrastructural studies showed profound apoptotic features in bone marrow progenitor cells in CN. Colony-forming assays demonstrated a 75% decrease in the number of early myeloid-committed colonies compared with controls. Long-term culture-initiating cell assays demonstrated a 6-fold increase in production of primitive progenitor cells in CN. To determine whether accelerated apoptosis might account for the underproduction of myeloid progenitors, the hematopoietic subpopulations were labeled with fluorescein isothiocyanate-annexin V and analyzed by flow cytometry. Short-term culture of CN cells resulted in apoptosis of approximately 65% of CD34(+) cells, 80% of CD33(+)/CD34(-) cells, and more than 70% of CD15(+) cells, as compared with 20%, 7%, and 15% apoptosis in respective control subpopulations. Evidence of accelerated apoptosis of bone marrow progenitor cells was observed in all 8 patients participating in the study, regardless of the stage in the CN cycle in which bone marrow aspirations were obtained. Granulocyte colony-stimulating factor therapy of CN patients significantly improved survival of bone marrow progenitor cells. These data indicate that ineffective production of neutrophils is due to accelerated apoptosis of bone marrow myeloid progenitor cells in CN.

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Section: R E T R a C T E D O N J U L Y 3 2 0 1mentioning

confidence: 99%

Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia

Aprikyan

Liles

Rodger

et al. 2001

Blood

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“…Abnormal accumulation of apoptotic cells results in chronic tissue damage and persistent inflammation [98,120]. Indeed, apoptosis of dying inflammatory cells is an integral step in the ending of inflammatory response, and failure of this process may have detrimental effects on airways [98,121].…”

Section: Macrophagesmentioning

confidence: 99%

Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms

Fuschillo¹,

Felice²,

Balzano³

2008

European Respiratory Journal

184

124

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Bronchiectasis is a chronic and debilitating lung disease, characterised by irreversible dilatation of the bronchi as consequence of airway injury and remodelling due to recurrent or chronic airway inflammation and infection. The underlying aetiologies include autoimmune diseases, severe infections, genetic abnormalities and acquired disorders.The pathogenesis of bronchiectasis is poorly understood. Three distinct pathogenetic elements, namely infection, inflammation and enzymatic actions, which interact with each other, have been implicated in the pathophysiology of bronchiectasis.Some recent observations indicate that airway inflammation in bronchiectasis comes from a deregulated cytokine network independent of bacterial airway colonisation.In the present review, current knowledge about cellular and molecular inflammatory events in the dynamic process of host-pathogen interaction that are thought to play a relevant role in the pathogenic mechanisms of airway wall destruction leading to bronchiectasis are discussed.

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“…9 Dysregulation of granulocyte apoptosis results in abnormal accumulation of cells and may result in chronic tissue damage and persistent inflammation. 10 Subsequent clearance of the apoptotic granulocyte is a critical feature of the apoptotic process. 11 Secondary necrosis of apoptotic cells is likely to occur if phagocytic clearance is disrupted resulting in amplification of inflammation.…”

mentioning

confidence: 99%

Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis

Watt

Brown²,

Courtney³

et al. 2004

Thorax

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Emerging role of apoptosis in the pathogenesis of severe neutropenia

Cited by 12 publications

References 9 publications

Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia

Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia

Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms

Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis

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