Priming of Blood Neutrophils in Children with Cystic Fibrosis: Correlation between Functional and Phenotypic Expression of Opsonin Receptors before and after Platelet‐Activating Factor Priming

Witko‐Sarsat, Véronique; Halbwachs‐Mecarelli, Lise; Sermet‐Gaudelus, Isabelle; Bessou, Gilles; Lenoir, G.; Allen, Robert C.; Descamps‐Latscha, Béatrice

doi:10.1086/314532

Cited by 28 publications

(25 citation statements)

References 46 publications

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“…Cystic fibrosis patients also have increased oxidative stress [23] due to neutrophils [24] and consequently have been shown to have lower levels of antioxidants in the circulation [25,26]. Studies on isolated neutrophils from the peripheral blood of CF patients have shown a different response pattern to inflammatory mediators and stimulants to that seen in neutrophils from normals [10,11,27]. In this study, the spontaneous superoxide generation from neutrophils from CF patients was not significantly different after resolution of the exacerbation compared to before treatment.…”

Section: Discussionmentioning

confidence: 55%

“…Neutrophils isolated from CF patients display a different pattern of response to inflammatory mediators to that observed from normals [10,11]. For example, neutrophils and eosinophils isolated from CF patients have been shown to have an altered arachidonic acid turnover [12], and an increased release of myeloperoxidase (MPO), eosinophil cationic protein (ECP), and eosinophil protein X (EPX) [13].…”

Section: Introductionmentioning

confidence: 99%

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Effect of cystic fibrosis exacerbations on neutrophil function

Brockbank

Downey

Elborn

et al. 2005

International Immunopharmacology

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In cystic fibrosis (CF), inflammation is caused by persistent bacterial infection from Pseudomonas aeruginosa and Burkholderia cenocepacia in the lung and is characterised by the persistent infiltration of massive numbers of neutrophils which leads to lung injury. The aim of this present study was to investigate the effects of CF exacerbations on the reactivity of peripheral blood neutrophils compared to data from a normal healthy control population. Peripheral blood neutrophils were isolated from control subjects and CF patients before and after an exacerbation of their lung disease. Isolated neutrophils were stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA) and the rate of superoxide generation and elastase activity measured and compared with neutrophils from healthy age-matched controls. Neutrophils from CF patients spontaneously generated higher levels of superoxide after resolution of the exacerbation compared to control neutrophils. The stimulated generation of superoxide from control neutrophils was not significantly different from neutrophils isolated from CF patients either before or after resolution of the CF exacerbation. Neutrophils from CF patients spontaneously released more elastase than control neutrophils but released less elastase than control neutrophils in response to fMLP. The stimulated release of elastase from neutrophils was not significantly different before compared to after resolution of the exacerbation. Neutrophils from CF patients displayed a different pattern of response than those from control subjects; however, CF exacerbations did not appear to modulate neutrophil function. D

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Effect of cystic fibrosis exacerbations on neutrophil function

Brockbank

Downey

Elborn

et al. 2005

International Immunopharmacology

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“…The methodology and reagents were described in detail previously (23). Briefly, eosinophils were enriched from monodispersed thymocytes as described above.…”

Section: Measurement Of Nadph Oxidase and Peroxidase Activitiesmentioning

confidence: 99%

CD11c+ Eosinophils in the Murine Thymus: Developmental Regulation and Recruitment upon MHC Class I-Restricted Thymocyte Deletion

Throsby

Herbelin

Pleau

et al. 2000

The Journal of Immunology

111

100

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Eosinophils are bone marrow-derived cells released into the circulation during hypersensitivity reactions and parasitic infections. Under normal conditions most eosinophils are tissue bound, where their physiologic role is unclear. During in situ analysis of the thymic microenvironment for CD11c+ dendritic cell subpopulations (APC critical in the process of thymic negative selection) a discrete population of CD11b/CD11c double-positive cells concentrated in the cortico-medullary region of young mice was detected. Thymic CD11c+ cells were isolated, and the CD11b+ subpopulation (CD44high, class IIlow, CD11cint) was identified as mature eosinophils based on: scatter characteristics, major basic protein mRNA expression, and eosinophilic granules. They are hypodense, release high levels of superoxide anion, and express CD25, CD69, and mRNA for IL-4 and IL-13, but not GM-CSF or IL-5, suggesting a distinct state of activation. Thymic eosinophils are preferentially recruited during the neonatal period; absolute numbers increased 10-fold between 7–14 days to reach parity with dendritic cells before diminishing. In a model of acute negative selection, eosinophil numbers were increased 2-fold 6 h after cognate peptide injection into MHC class I-restricted female H-Y TCR transgenic mice. In both peptide-treated female and negatively selecting male H-Y TCR mice, clusters of apoptotic bodies were associated with eosinophils throughout the thymus. Our data demonstrate a temporal and spatial association between eosinophil recruitment and class I-restricted selection in the thymus, suggesting an immunomodulatory role for eosinophils under nonpathological conditions.

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“…Particularly, circulating PMNs from CF patients appear to be primed and can release increased levels of interleukin (IL)-8 (3), elastase (4), lipoxygenase products (5), myeloperoxidase (6), and chloramine (7) in response to proper activators. Furthermore, CF blood PMNs display enhanced oxidative activity in response to platelet-activating factor and untreated or opsonized zymosan (8). In contrast, circulating PMNs display a decreased chemotactic response to leukotriene B4 (9) and decreased chlorination of phagocytosed bacteria (1).…”

Section: Introductionmentioning

confidence: 99%