Effects of Heat Shock and Hypoxia on Neonatal Neutrophil Lipopolysaccharide Responses: Altered Apoptosis, Toll-Like Receptor-4 and CD11b Expression Compared with Adults

Molloy, Eleanor J.; O’Neill, Amanda; Doyle, Belinda T.; Grantham, Julie J; Taylor, Cormac T.; Sheridan-Pereira, Margaret; Fitzpatrick, John M.; Webb, David; Watson, R. William G.

doi:10.1159/000091743

Cited by 22 publications

(23 citation statements)

References 53 publications

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“…In contrast, the synergism between LPS and MV was not present in the juvenile mice, suggesting that important interactions between innate immunity and responses to mechanical stretch in the lungs are acquired with age. These findings are consistent with previous studies in rodents showing that newborns have lesser inflammatory and injury responses to hypoxia, MV, and LPS as compared with adults (13,18,19,33). These data are broadly consistent with clinical observations suggesting that children have a lower incidence and a better outcome from ALI than adults (1, 3).…”

Section: Discussionsupporting

confidence: 92%

“…Apoptosis is an important process in normal lung development as well as in lung injury and repair (57,58). B-cell leukemia/lymphoma 2 (Bcl2) and mitogen-activated kinases (MAPK) have been shown to be important in mediating antiinflammatory and antiapoptotic responses to hypo-and hyperoxia, lipopolysaccharide, and mechanical stretch (33,55,(59)(60)(61). Amyloid b-protein precursor (App) has been shown to suppress FE65 (a neural adaptor protein) mediated apoptosis in neurons (62), but the role of this pathway in the lungs is not known.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Age on the Synergistic Interactions between Lipopolysaccharide and Mechanical Ventilation in Mice

Smith

Gharib

Frevert

et al. 2010

Am J Respir Cell Mol Biol

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Children have a lower incidence and mortality from acute lung injury (ALI) than adults, and infections are the most common event associated with ALI. To study the effects of age on susceptibility to ALI, we investigated the responses to microbial products combined with mechanical ventilation (MV) in juvenile (21-d-old) and adult (16-wk-old) mice. Juvenile and adult C57BL/6 mice were treated with inhaled Escherichia coli 0111:B4 lipopolysaccharide (LPS) and MV using tidal volume 5 15 ml/kg. Comparison groups included mice treated with LPS or MV alone and untreated age-matched control mice. In adult animals treated for 3 hours, LPS plus MV caused synergistic increases in neutrophils (P , 0.01) and IgM in bronchoalveolar lavage fluid (P 5 0.03) and IL-1b in whole lung homogenates (P , 0.01) as compared with either modality alone. Although juvenile and adult mice had similar responses to LPS or MV alone, the synergistic interactions between LPS and MV did not occur in juvenile mice. Computational analysis of gene expression array data suggest that the acquisition of synergy with increasing age results, in part, from the loss of antiapoptotic responses and the acquisition of proinflammatory responses to the combination of LPS and MV. These data suggest that the synergistic inflammatory and injury responses to inhaled LPS combined with MV are acquired with age as a result of coordinated changes in gene expression of inflammatory, apoptotic, and TGF-b pathways.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Effects of Age on the Synergistic Interactions between Lipopolysaccharide and Mechanical Ventilation in Mice

Smith

Gharib

Frevert

et al. 2010

Am J Respir Cell Mol Biol

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“…Increases in maternal blood levels of the complement component C3b, CD11b/CD18 adhesion molecules, and IL-8 receptors are also observed during labor, and these may contribute to decreased neutrophil apoptosis (6). Hypoxia, which can occur transiently during labor, also suppresses neutrophil apoptosis (7)(8)(9). It has been suggested that the antiapoptotic effects of inflammatory mediators and of hypoxia are due, in part, to up-regulation of proteins such as IAP-2, which block the activity of proapoptotic caspases (10).…”

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confidence: 99%

Influence of Labor on Neonatal Neutrophil Apoptosis, and Inflammatory Activity

et al. 2007

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“…Each sample was acquired over 2 min at medium speed, and a minimum of 5,000 events were collected and analyzed. All measurements were performed under the same instrument settings (39).…”

Section: Quantification Of Intracellular Roi Productionmentioning

confidence: 99%

“…Articles agent LPS 1 μg/ml to mimic an inflammatory response in vitro (39). Samples were analyzed using an Accuri C6 flow cytometer with a CFlow Plus software.…”

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confidence: 99%

Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants

et al. 2015

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Articles neuroimaging. We examined markers of monocyte and neutrophil function and activation (CD11b (activation), TLR-4 expression (LPS recognition), and ROI production (function)) serially over the first week of life and correlated our findings with neuroimaging. RESULTS Patient DemographicsFifty-one preterm infants born <32 wk gestation were included, and three infants died (normal neuroimaging n = 40; abnormal neuroimaging/ Death (RIP); n = 11). A total of 404 samples were processed. There were no differences in gender distribution, preeclampsia, prolonged rupture of membranes, maternal pyrexia, histological chorioamnionitis, surfactant treatment, gestational age, birth weight, mode of delivery, doses of antenatal steroids received, Apgar scores, cord or admission blood gas parameters, nasal continuous positive airway pressure (CPAP) hour, or duration of intubation, between preterm neonates with normal and abnormal neuroimaging ( Table 1). There was a statistically significant difference in mortality (n (%)) observed between the two groups: normal vs. abnormal neuroimaging 0 (0) vs. 3 (21) (P = 0.04).All infants had serial cranial ultrasounds, and 29 infants had a magnetic resonance imaging (MRI) brain at term corrected age. MRI was scored according to the Inder criteria (6) independently by a consultant Pediatric Radiologist. Twenty infants had completely normal imaging (white matter (WM) score = 5-6; gray matter (GM) score 3-5). Nine infants had evidence of WM abnormality (mild = 4: WM score 7-9; moderate = 3: WM score 10-12; severe = 2: WM score 13-15). One infant had both WM and GM abnormality (GM score 6-9; Tables 2 and 3). Twenty-two infants had only cranial ultrasound imaging. No abnormality was detected in 14 infants. Evidence of intraventricular hamorrhage (IVH) was detected in five infants (grade 1 = 4; grade 2 = 1). Three infants had increased echogenicity in the periventricular WM.There were no other significant differences between the study groups with respect to chronic lung disease, patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity, late-onset sepsis (LOS), and number of septic episodes and antibiotic days. There were no significant differences in duration of intubation, intermittent positive pressure ventilation, nasal CPAP or nasal prong oxygen hours required, duration of free flow oxygen delivery, or maximum inspired oxygen requirements during neonatal intensive care unit stay in our study population. Neonatal Neutrophil and Monocyte ROI ProductionPreterm infants with abnormal neuroimaging produced significantly increased baseline intracellular neutrophil ROIs on day one of life compared with preterm controls (P = 0.023). There was a statistically significant increase in baseline ROI production in control preterms at 24-48 h (P = 0.047) and preterms with abnormal neuroimaging at 0-24 h of life (P =0.037) compared with adults (Figure 1a). Irrespective of neuroimaging outcome, all preterms were LPS responsive and had increased ROI production following ex vivo LPS...

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Effects of Heat Shock and Hypoxia on Neonatal Neutrophil Lipopolysaccharide Responses: Altered Apoptosis, Toll-Like Receptor-4 and CD11b Expression Compared with Adults

Cited by 22 publications

References 53 publications

Effects of Age on the Synergistic Interactions between Lipopolysaccharide and Mechanical Ventilation in Mice

Effects of Age on the Synergistic Interactions between Lipopolysaccharide and Mechanical Ventilation in Mice

Influence of Labor on Neonatal Neutrophil Apoptosis, and Inflammatory Activity

Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants

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