Neutrophil and cytokine activation with neonatal extracorporeal membrane oxygenation

Fortenberry, James D.; Bhardwaj, Vijay Kumar; Niemer, Paula; Cornish, J. Devn; Wright, Jean Ann; Bland, Lee A.

doi:10.1016/s0022-3476(96)80133-8

Cited by 101 publications

(106 citation statements)

References 29 publications

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“…In some patients, such exposure may cause activation of a systemic inflammatory reaction. 23,24 We hypothesize that this could have resulted in the recruitment of multiple cell types, including endothelial and MSCs. Future studies are needed to describe expected frequency of ECFCs and MSCs in healthy term newborns as well as in critically ill neonates not requiring ECMO and to investigate their role in a variety of disease processes observed in neonates.…”

Section: Discussionmentioning

confidence: 99%

Endothelial colony-forming cells and mesenchymal stem cells from ECMO circuits of term infants

et al. 2010

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Objective: Endothelial progenitor cells (EPCs) have been examined in numerous adult diseases and have been suggested as a cellular-based therapy. However, there are no reports describing EPCs being isolated from newborn peripheral blood.Study Design: Endothelial colony-forming cells (ECFCs), a subtype of EPCs, were isolated from blood collected from 12 neonatal extracorporeal membrane oxygenation (ECMO) circuits.Result: ECFCs were isolated in all samples. We unexpectedly isolated a distinctly different colony of mesenchymal stem cells (MSCs) in seven samples. Both cell types expressed the expected endothelial or mesenchymal cell surface antigens. Conclusion:To our knowledge, this is the first report of ECFCs and MSCs isolated from peripheral blood of critically ill term newborns. Both cells types may be mobilized in response to critical illness or to the ECMO circuit. Further studies evaluating the role of stem cells in various newborn conditions are warranted.

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Section: Discussionmentioning

confidence: 99%

Endothelial colony-forming cells and mesenchymal stem cells from ECMO circuits of term infants

et al. 2010

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“…They also found that diminished neonatal neutrophil transendothelial migration was related, not only to quantitative abnormalities in CD11b, but also to functional deficits in stimulated binding to the ligand, ICAM-1. CD11b up-regulation has been reported in the clinical setting of neonatal sepsis (29,30) and extracorporeal membrane oxygenation (31).…”

Section: Discussionmentioning

confidence: 99%

Comparison of L-Selectin and CD11b on Neutrophils of Adults and Neonates during the First Month of Life

KIM

2003

Pediatric Research

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The newborn infant is particularly susceptible to infection in the first weeks of life and this may be, in part, related to functional impairment of neonatal neutrophils in regard to adherence, chemotaxis, and migration. Differences in expression of the neutrophil adherence molecules, L-selectin and CD11b/CD18 (Mac-1), have been previously demonstrated in cord blood and in very young infants (Յ 48 h) compared with adults, but it is unknown for how long these differences persist. We measured surface expression of neutrophil L-selectin and CD11b using flow cytometry in healthy term human newborns from 24 h through 4 wk of age. We also measured levels of soluble L-selectin using an ELISA in neonates though the age of 4 wk. Compared with adults, neonates expressed significantly less L-selectin on resting neutrophils through 4 wk of age, with the lowest levels being at 24 h. Expression of L-selectin on the neutrophil after activation with N-formyl-methionyl-leucyl-phenylalanine was less in the neonate than in the adult (p Ͻ 0.05) for the first week of life. Soluble L-selectin showed a steady increase with age in the neonates. Soluble L-selectin was significantly lower in the 24-h neonate compared with the adult and was higher in the 4-wk neonate compared with the adult. CD11b expression was similar between neonates and adults on unstimulated neutrophils, but upon activation, the neonatal neutrophil demonstrated significantly lower up-regulation of CD11b on the neutrophil surface through 4 wk of age compared with adults (p Ͻ 0.05 for all ages except 1 wk). These findings that differences in expression of L-selectin and CD11b from that in adults persist throughout the neonatal period provide further evidence that these differences may play a role in the neutrophil defects observed during the neonatal period. The newborn infant is particularly susceptible to severe bacterial and fungal infections (1, 2). It is unknown for how long this susceptibility persists, but it is a clinical practice to treat these infants as immunocompromised for at least the length of the neonatal period (first 28 d of life). Neonatal neutrophils, compared with those of adults, have been found to have functional impairments in their ability to adhere to an activated endothelial surface and to migrate in response to chemotaxins (2-6). These impairments may delay or prevent neutrophils from reaching inflammatory sites, thus inhibiting the ability of the neonate to effectively fight infection.Adherence of neutrophils to the vascular endothelium is an early step in the process of neutrophil migration into inflamed tissue and is mediated by proteins expressed on the surface of the neutrophil and the endothelium. Members of two important families of adhesion molecules located on the surface of the neutrophil are L-selectin and the ␤2-integrins. L-Selectin is found on neutrophils and other leukocytes and recognizes carbohydrate ligands on the endothelial cell, including sialyl Lewis (7). L-Selectin is thought to mediate, along with other selectin prote...

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“…During ECMO treatment, an inflammatory reaction with neutropenia (2), activation of PMN (3), and a capillary leak syndrome with systemic and pulmonary edema (4,5) have been described. However, it is not clear, to what extent this changes result from the patient's disease (6) or from the effects of extracorporeal circulation of the blood.…”

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confidence: 99%

“…The induction of an inflammatory response and the loss of endothelial integrity represent a hallmark of the capillary leakage commonly observed in CPB (7) and neonatal ECMO (4,5), with systemic and pulmonary edema often prolonging the duration of ECMO. In spite of evidence for activation of PMN in neonatal ECMO (3), it is unclear to what extent this activation is due to the underlying disease or the leukocyte-synthetic surface interaction and whether this activation is linked to the clinically observed changes in endothelial cell barrier function.…”

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confidence: 99%

Leukocyte and Endothelial Activation in a Laboratory Model of Extracorporeal Membrane Oxygenation (ECMO)

et al. 2000

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An inflammatory response and a capillary leak syndrome frequently develop during the treatment of neonatal respiratory failure by extracorporeal membrane oxygenation (ECMO). The present study was performed to investigate leukocyte activation and endothelial cell dysfunction that are associated with prolonged contact of blood components with synthetic surfaces. Laboratory ECMO was performed with fresh human blood at 37°C for 8 h (n ϭ 6). Leukocyte activation was measured by L-selectin (CD62L) and CD18 integrin surface expression and by neutrophil-derived elastase release. To monitor endothelial activation, endothelial cell ICAM-1 (CD54) expression was measured in cultured endothelial cells from human umbilical veins (HUVEC) after incubation with plasma from the ECMO experiments. CD18 integrin expression was found significantly upregulated on polymorphonuclear neutrophils and monocytes after 2-4 h of laboratory ECMO. L-selectin was reduced on both cell types during the total duration of the experiments. Soluble L-selectin (sCD62L) and total and differential leukocyte counts remained unchanged during the experiment. Neutrophil-derived elastase content was maximal after 8 h of ECMO. Plasma from the ECMO experiments did not induce ICAM-1 expression of cultured HUVEC. We conclude that prolonged contact with synthetic surfaces during ECMO activates phagocytes, which may contribute to the inflammatory response seen in ECMOtreated patients. Activated phagocytes do not accumulate in the extracorporeal system nor release humoral factors inducing ICAM-1 expression on endothelial cells. ECMO is the standard treatment for newborn infants with respiratory failure unresponsive to conventional pulmonary support (1). During ECMO treatment, an inflammatory reaction with neutropenia (2), activation of PMN (3), and a capillary leak syndrome with systemic and pulmonary edema (4, 5) have been described. However, it is not clear, to what extent this changes result from the patient's disease (6) or from the effects of extracorporeal circulation of the blood. We therefore performed laboratory ECMO without connecting the system to a patient, to study the isolated effects of prolonged extracorporeal circulation of blood on leukocyte number, expression of leukocyte adhesion molecules, and the release of mediators that might activate endothelial cells.During hemodialysis or cardiopulmonary bypass (CPB), leukocytes are activated (2, 7, 8) and humoral mediators are generated, which impairs endothelial cell integrity (9 -11). The induction of an inflammatory response and the loss of endothelial integrity represent a hallmark of the capillary leakage commonly observed in CPB (7) and neonatal ECMO (4, 5), with systemic and pulmonary edema often prolonging the duration of ECMO. In spite of evidence for activation of PMN in neonatal ECMO (3), it is unclear to what extent this activation is due to the underlying disease or the leukocyte-synthetic surface interaction and whether this activation is linked to the clinically observed changes in endothel...

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Neutrophil and cytokine activation with neonatal extracorporeal membrane oxygenation

Cited by 101 publications

References 29 publications

Endothelial colony-forming cells and mesenchymal stem cells from ECMO circuits of term infants

Endothelial colony-forming cells and mesenchymal stem cells from ECMO circuits of term infants

Comparison of L-Selectin and CD11b on Neutrophils of Adults and Neonates during the First Month of Life

Leukocyte and Endothelial Activation in a Laboratory Model of Extracorporeal Membrane Oxygenation (ECMO)

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