Neutrophil Production and Function in Newborn Infants

Carr, Robert

doi:10.1046/j.1365-2141.2000.01992.x

Cited by 192 publications

(177 citation statements)

References 144 publications

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“…We determined that 0-h cord blood PMN had a greater elaboration of ROI in response to phorbol ester stimulation compared with adult PMN, an observation also made by other investigators (32,35,36). After 24 h of culture, ROI elaboration was proportionately decreased in nonapoptotic PMN from both groups.…”

supporting

confidence: 56%

“…Neonatal PMN have a variety of functional impairments (26,27,31,32) that might be related to incomplete terminal differentiation, as suggested by observations that segmented PMN in the bone marrow are functionally immature compared with those in the circulation (33). Cord blood has been observed to contain a mixed population of immature and mature PMN, and lower expression of CD11b was associated with decreased PMN maturity (34).…”

mentioning

confidence: 93%

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Neonatal Neutrophils with Prolonged Survival Exhibit Enhanced Inflammatory and Cytotoxic Responsiveness

et al. 2005

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Apoptosis is critical to the resolution of inflammation, as it promotes the removal of neutrophils (PMN) by the reticuloendothelial system. In contrast, PMN persistence characterizes the early stages of chronic inflammation. Adult PMN with delayed senescence retain some functionality, although this has not been described for neonatal PMN. We hypothesized that neonatal PMN with prolonged survival retain cytotoxic and inflammatory function. To test one aspect of inflammatory function, we determined surface CD11b expression on 0-h and 24-h PMN after chemotactic formyl-methionine-leucine-phenylalanine (fMLP) stimulation. Although fMLP induced a greater percentage upregulation of CD11b on 0-h adult PMN, this was similar between nonapoptotic cord blood and adult PMN at 24 h. Furthermore, percentage up-regulation of CD11b was more robust for 24-h than for 0-h cord blood PMN. In contrast, there was no difference in responsiveness between 0-h and 24-h adult PMN. In studies of cytotoxic potential, we determined the expression of reactive oxygen intermediates (ROI) in phorbol 12-myristate 13-acetatestimulated cord blood and adult PMN at 0 h and in 24-h nonapoptotic PMN, using the dihydrorhodamine 123 assay.Stimulated cord blood PMN generated more ROI than did adult PMN at both 0 h and 24 h; in addition, ROI levels in 24-h cord blood PMN were similar to those of 0-h adult PMN. We conclude that PMN with prolonged survival retain specific cytotoxic and inflammatory functions, and these are enhanced in cord blood PMN. We speculate that neonatal PMN with prolonged survival have the functional capacity to contribute to the pathogenesis of inflammatory disorders. Abbreviations CLD, chronic lung disease DHR, dihydrorhodamine 123 fMLP, formyl-methionine-leucine-phenylalanine PE, phycoerythrin PMA, phorbol 12-myristate 13-acetate PMN, neutrophil(s) ROI, reactive oxygen intermediates 7-AAD, 7-aminoactinomycin PMN serve as the primary line of host defense during the early stages of sepsis and inflammation (1). After activation by systemic or local factors, primed endothelial cells interact with PMN through adhesion molecules that include selectins and integrins (2). These adhesive interactions initiate a process that allows the extravasation of PMN into inflamed tissue with the goal of neutralizing the inciting stimulus. In the case of inflammation mediated by bacterial or fungal microorganisms, phagocytosis and subsequent killing of these invaders occurs through mechanisms that partly involve ROI and proteases (3,4).The concept that apoptosis of inflammatory PMN and their timely removal by resident macrophages are critical to the resolution of inflammation has been well established (5,6). During the resolution phase, PMN typically undergo the phenotypic changes associated with apoptosis, which promotes their removal by resident macrophages (7). PMN can also undergo necrosis and lysis, a process that induces cytotoxicity in surrounding tissues (8), although apoptosis is the more common and physiologically preferable route. All cells a...

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supporting

confidence: 56%

mentioning

confidence: 93%

Neonatal Neutrophils with Prolonged Survival Exhibit Enhanced Inflammatory and Cytotoxic Responsiveness

et al. 2005

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“…Indeed, the host-defense deficiency posed by a low neutrophil count in these patients might be compounded by reduced neutrophil function. Ineffective chemotaxis is probably the best-studied neutrophil deficiency of preterm neonates, 30 but extensive studies of neutrophil function in ELBW neonates have not been reported.…”

Section: Discussionmentioning

confidence: 99%

Low blood neutrophil concentrations among extremely low birth weight neonates: data from a multihospital health-care system

Christensen

Henry²,

Wiedmeier

et al. 2006

J Perinatol

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“…The susceptibility of neonates to serious bacterial and fungal infections is related, in part, to quantitative and qualitative neutrophil deficiencies (2). Neutrophil migration, or chemotaxis, involves the recruitment of neutrophils from the circulation, their adherence to vascular endothelial cells, and their migration through the vessel wall to the site of microbial invasion (3).…”

mentioning

confidence: 99%

Circulating Concentrations of Chemokines in Cord Blood, Neonates, and Adults

et al. 2002

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Chemokines are critical for the movement of leukocytes. Chemotaxis is deficient in neonates, particularly those delivered prematurely, and this likely contributes to their increased vulnerability to sepsis. The concentrations of circulating chemokines in neonates have not been reported, nor is it known whether low chemokine concentrations contribute to their defective chemotaxis. We hypothesized that serum concentrations of chemokines 1) would be lower in preterm than term neonates, and 2) would be lower in preterm and term neonates than adults. Samples were obtained from preterm and term neonates with normal neutrophil and eosinophil counts, umbilical cord blood samples from pregnancies without clinical evidence of intra-amniotic infection, and healthy adult volunteers. The concentrations of epithelial neutrophil activating peptide-78, growth-related oncogene-␣, eotaxin, RANTES (regulated upon activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1␣ were measured using specific ELISA. Serum concentrations from preterm infants were either similar to or higher than those measured in term neonates and adults. We conclude that the chemotactic defect observed in premature neonates is not the result of diminished circulating concentrations of any of the specific chemokines we measured. Neonatal sepsis is a life-threatening event affecting 3-5 neonates per 1000 live births (1). The susceptibility of neonates to serious bacterial and fungal infections is related, in part, to quantitative and qualitative neutrophil deficiencies (2). Neutrophil migration, or chemotaxis, involves the recruitment of neutrophils from the circulation, their adherence to vascular endothelial cells, and their migration through the vessel wall to the site of microbial invasion (3). Important elements in this process are the chemotactic cytokines collectively known as chemokines. These are members of a family of homologous proteins with molecular weights in the range of 8 -12 kD (4, 5).IL-8 is the most extensively studied chemokine in neonates (6), but no information exists regarding the circulating concentrations of other leukocyte-specific chemokines during the neonatal period. Because preliminary in vitro studies suggest that perturbations in the concentration of chemokines are, in part, responsible for deficiencies in leukocyte chemotaxis (7), we quantified the circulating concentrations of specific leukocyte chemokines in cord blood sera/plasma and in the sera/ plasma of uninfected preterm and term neonates. On the basis of the chemotactic deficiencies of neonates, we hypothesized that the serum concentrations of leukocyte chemokines would 1) be lower in preterm neonates than in term neonates and 2) be lower in term neonates than in adults. Using specific ELISA, we measured the concentrations of neutrophil-specific ␣-chemokines-ENA-78 and GRO-␣-as well as eosinophil-, basophil-, and monocyte-specific ␤-chemokines-RANTES, eotaxin, and MIP-1␣. MATERIALS AND METHODS SubjectsPreterm (n ϭ 50) and term neonates (n...

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Neutrophil Production and Function in Newborn Infants

Cited by 192 publications

References 144 publications

Neonatal Neutrophils with Prolonged Survival Exhibit Enhanced Inflammatory and Cytotoxic Responsiveness

Neonatal Neutrophils with Prolonged Survival Exhibit Enhanced Inflammatory and Cytotoxic Responsiveness

Low blood neutrophil concentrations among extremely low birth weight neonates: data from a multihospital health-care system

Circulating Concentrations of Chemokines in Cord Blood, Neonates, and Adults

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