The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates

Published on Apr 1, 2013in Pediatric Research3.756
路 DOI :10.1038/PR.2012.196
Christian Gille17
Estimated H-index: 17
,
Stephan Dreschers7
Estimated H-index: 7
(Boston Children's Hospital)
+ 8 AuthorsThorsten W. Orlikowsky16
Estimated H-index: 16
Sources
Abstract
The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates
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References37
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#1William J. JanssenH-Index: 49
#2Lea Barthel (University of Colorado Denver)H-Index: 13
Last. Peter M. Henson (University of Colorado Denver)H-Index: 126
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Rationale: During acute lung injury (ALI) the macrophage pool expands markedly as inflammatory monocytes migrate from the circulation to the airspaces. As inflammation resolves, macrophage numbers return to preinjury levels and normal tissue structure and function are restored. Objectives: To determine the fate of resident and recruited macrophages during the resolution of ALI in mice and to elucidate the mechanisms responsible for macrophage removal. Methods: ALI was induced in mice using influ...
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#3M. R. Adams (UZH: University of Zurich)H-Index: 186
Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years' corrected age in extremely preterm infants.
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#1Alan Leviton (Boston Children's Hospital)H-Index: 92
#2Jonathan L. Hecht (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 57
Last. Olaf Dammann (Tufts University)H-Index: 70
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Abstract Intrauterine inflammation is followed by elevated concentrations of inflammation-related proteins in the newborn's blood. Many of these proteins have short half-lives. The persistence of this postnatal inflammation has not previously been investigated. In a sample of 834 infants born before the 28th week of gestation, 12% (103) had grade 1 or 2, and 17% (142) had grade 3, 4, or 5 umbilical cord inflammation. Concentrations of nine proteins previously shown to be associated with umbilica...
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#1Alan Leviton (Boston Children's Hospital)H-Index: 92
#2Raina N. Fichorova (Brigham and Women's Hospital)H-Index: 60
Last. Nigel Paneth (MSU: Michigan State University)H-Index: 87
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Abstract Background We wanted to assess to what extent concentrations of circulating proteins appear to be developmentally regulated, and to what extent such regulation is influenced by intra-uterine inflammation. Methods We measured 22 proteins in blood obtained on postnatal days 1, 7, and 14 from 818 children born before the 28th week of gestation for whom we also had information about placenta morphology. Results Within the narrow gestational age range of this sample, some protein concentrati...
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#1Thomas Schmitz (Charit茅)H-Index: 17
Last. Axel HeepH-Index: 26
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Perinatal brain damage may result in impaired neurological development in extremely preterm infants. The underlying pathophysiological mechanisms are complex, and biomarkers of prognostic value are not available. The aim of this study was to analyze soluble Fas (sFas) concentrations in the cerebrospinal fluid (CSF) representative for involvement of apoptotic processes in preterm infants developing posthemorrhagic hydrocephalus (PHHC) and to link them to white matter damage (WMD) diagnosed by cra...
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#1Wolfgang Thomas (Boston Children's Hospital)H-Index: 5
Chorioamnionitis as a major risk factor for spontaneous preterm birth, especially at earlier gestational ages, contributes to prematurity-associated mortality and morbidity. A gestation-independent effect of chorioamnionitis on neonatal outcome is much more difficult to assess. The influence of chorioamnionitis on neonatal outcome has become less evident with advances in neonatal care. A short-term beneficial effect of histological, but not clinical chorioamnionitis on incidence and severity of ...
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#1Barbara J. Stoll (Emory University)H-Index: 110
#2Nellie I. HansenH-Index: 34
Last. Waldemar A. Carlo (UAB: University of Alabama at Birmingham)H-Index: 103
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OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22鈥28 weeks) and very low birth weight (401鈥1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS: Rates...
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#1Fanny Turrel-DavinH-Index: 7
#2Caroline GuignantH-Index: 12
Last. Fabienne VenetH-Index: 44
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Introduction: Lymphocyte apoptosis has been suggested to play a central role in sepsis pathophysiology, and studies in animal models demonstrated that blocking this pathway improves outcome. However, no routine biomarkers of apoptosis are so far available in patients. Thus, the aim of our study was to assess the different biomarkers of apoptosis putatively usable on a routine basis in septic shock. Methods: Thirteen septic shock patients (sampled twice between days 1 to 2 and days 3 to 5 after d...
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#1Monique E. De Paepe (Brown University)H-Index: 25
#2Sheila A. Haley (Brown University)H-Index: 13
Last. Quanfu Mao (Brown University)H-Index: 14
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We determined the time-specific effects of FasL overexpression on perinatal alveolar type II cell growth kinetics. To achieve temporal overexpression of respiratory epithelium-specific FasL expression, tetracycline inducible CCSP-rtTA/FasL-TetOp transgenic mice were given doxycycline (Dox) from gestational d 14 (E14) to E19 (antenatal treatment group), from postnatal d 1 (P1) to P7 (postnatal group), or from E14 to P7 (combined antenatal and postnatal group). Antenatal Dox administration induced...
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#1Ch. Gille (Boston Children's Hospital)H-Index: 1
#2Anja Leiber (Boston Children's Hospital)H-Index: 7
Last. Th. W. Orlikowsky (Boston Children's Hospital)H-Index: 1
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Background: Neonatal sepsis is characterized by an excessive inflammatory response induced by immune cells (monocytes). We investigated the initial stage of monocyte-pathogen interaction, i.e. bacterial ingestion and degradation at the single-cell level, by comparing a new flow cytometric procedure with culture methods. We also examined the hypothesis that, in terms of phagocytosis-induced cell death (PICD), phenotype, or cytokine production, cord blood monocytes (CBMO) differ from monocytes der...
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M桅 differentiate from circulating monocytes (Mo). The reduced ability of neonatal Mo to undergo apoptosis after E. coli infection (phagocytosis-induced cell death (PICD)) could contribute to sustained inflammatory processes. The objective of our study was to investigate whether immune metabolism in Mo can be modified to gain access to pro-apoptotic signaling. To this end, we supplemented Mo from neonates and from adults with the branched amino acid leucine. In neonatal Mo, we observed increased ...
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#1Christopher Platen (Boston Children's Hospital)H-Index: 4
#2Stephan Dreschers (Boston Children's Hospital)H-Index: 7
Last. Thorsten W. Orlikowsky (Boston Children's Hospital)H-Index: 16
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Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphireg...
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#3T M O'Shea (UNC: University of North Carolina at Chapel Hill)H-Index: 26
To identify specific risk factors for epilepsy for individuals born extremely preterm. In a prospective cohort study, at 10-year follow-up, children were classified as having epilepsy or seizures not associated with epilepsy. We evaluated for association of perinatal factors using time-oriented, multinomial logistic regression models. Of the 888 children included in the study, 66 had epilepsy and 39 had seizures not associated with epilepsy. Epilepsy was associated with an indicator of low socio...
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#1Stephan Dreschers (Boston Children's Hospital)H-Index: 7
#2Christopher Platen (Boston Children's Hospital)H-Index: 4
Last. Thorsten W. Orlikowsky (Boston Children's Hospital)H-Index: 16
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Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-伪-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli inf...
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#1Christopher Platen (Boston Children's Hospital)H-Index: 4
#2Stephan Dreschers (Boston Children's Hospital)H-Index: 7
Last. Thorsten W. Orlikowsky (Boston Children's Hospital)H-Index: 16
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Neonates are highly susceptible to microbial infections which is partially attributable to fundamental phenotypic and functional differences between effector cells of the adult and neonatal immune system. The resolution of the inflammation is essential to return to tissue homeostasis, but given that various neonatal diseases, such as periventricular leukomalacia, necrotizing enterocolitis, or bronchopulmonary dysplasia, are characterized by sustained inflammation, newborns seem predisposed to a ...
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#1Stephan Dreschers (Boston Children's Hospital)H-Index: 7
#2Christian GilleH-Index: 17
Last. Thorsten W. OrlikowskyH-Index: 16
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Phagocytosis-induced cell death (PICD) is diminished in cord blood monocytes (CBMO) as compared to cells from adults (PBMO) due to differences in the CD95-pathway. This may support a prolonged pro-inflammatory response with sequels of sustained inflammation as seen in neonatal sepsis. Here we hypothesized that TNF-伪 mediated induction of apoptosis is impaired in CBMO due to differences in the TNFR1-dependent internalization. Monocytes were infected with Escherichia coli-GFP (E. coli-GFP). Monocy...
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#1Paula Scotland (Duke University)H-Index: 9
#2Susan Buntz (Duke University)H-Index: 2
Last. Andrew E. Balber (Duke University)H-Index: 20
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Abstract Background aims DUOC-01, a cell product being developed to treat demyelinating conditions, is composed of macrophages that arise from CD14 + monocytes in the mononuclear cell (MNC) population of banked cord blood (CB). This article demonstrates that expression of multiple gene products that promote remyelination is rapidly up-regulated during manufacturing of DUOC-01 from either MNC or purified CB CD14 + monocytes. Methods Cell cultures were initiated with MNC or with immunoselected CD1...
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#1Stephan Dreschers (Boston Children's Hospital)H-Index: 7
#2Peter SauppH-Index: 1
Last. Thorsten W. OrlikowskyH-Index: 16
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BACKGROUND: Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO). HYPOTHESIS: Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulati...
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#1S. Kingsley Manoj Kumar (JIPMER: Jawaharlal Institute of Postgraduate Medical Education and Research)H-Index: 2
#2B. Vishnu Bhat (JIPMER: Jawaharlal Institute of Postgraduate Medical Education and Research)H-Index: 21
Abstract The ontogeny of immunity during early life is of high importance as it shapes the immune system for the entire course of life. The microbiome and the environment contribute to the development of immunity in newborns. As immune responses in newborns are predominantly less experienced they are increasingly susceptible to infections. Though the immune cells in newborns are in 鈥榥aive鈥 state, they have been shown to mount adult-like responses in several circumstances. The innate immunity pla...
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#1M. Pierro (University of Milan)H-Index: 1
#2B. Th茅baud (Ottawa Hospital Research Institute)H-Index: 1
The imbalance of inflammatory and anti-inflammatory responses in favor of inflammation plays a major role in the pathogenesis of many neonatal diseases. Inflammation in the perinatal period carries important long-term consequences, including neurodevelopmental and respiratory complications. Treatments able to restore immune homeostasis may reduce neonatal mortality and prevent long-term deleterious multi-organ consequences of unchecked inflammation. Mesenchymal stromal cells are a heterogenous g...
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