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A model to study antioxidant regulation of endotoxemia-modulated neonatal granulopoiesis and granulocyte apoptosis. Pediatr Res 2000 Dec;48(6):829-34

Date

12/05/2000

Pubmed ID

11102554

DOI

10.1203/00006450-200012000-00021

Abstract

Neonates with septicemia tend to develop granulocytopenia, which may, in part, be due to septic mediators such as oxygen free radicals and tumor necrosis factor alpha (TNF-alpha). Granulocytopenia may be caused by a decrease in granulocyte growth and/or an increase in granulocyte destruction. In the present study, we investigated antioxidant regulation of endotoxin-modulated neonatal granulopoiesis and granulocyte apoptosis. Using human umbilical cord blood (HUCB), we found that simulating endotoxemia in vitro elicited significant superoxide production within a few minutes. Endotoxin exposure suppressed colony-forming unit-granulocyte and monocyte formation in a dose-dependent fashion. Addition of antioxidants such as N-acetyl-cysteine could reverse the endotoxin suppression of colony-forming unit-granulocyte and monocyte formation (13 +/- 5 versus 75 +/- 5 colony-forming units/mL). Spontaneous in vitro granulocyte apoptosis in 6 h, as reflected by phosphatidylserine expression on the cell surface, was higher in granulocytes from HUCB than in those from adult blood (10.8 +/- 1.0% versus 5.6 +/- 1.2%). The addition of endotoxin or IL-8 to the cells in the in vitro model did not promote granulocyte apoptosis, but TNF-alpha, a major mediator of the effects of endotoxin, significantly induced granulocyte apoptosis in HUCB (control versus TNF-alpha: 8.9 +/- 1.2% versus 35.9 +/- 2.9%). Addition of the antioxidant N-acetyl-cysteine effectively blocked TNF-alpha-induced granulocyte apoptosis as demonstrated by DNA fragmentation. Results from these studies indicate that oxygen radicals are directly involved in endotoxin suppression of granulopoiesis, and indirectly promote granulocyte apoptosis, presumably through TNF-alpha-mediated action. Thus, under certain conditions, modulation of oxygen radical production in the blood may benefit neonates with granulocytopenia.

Author List

Yang KD, Chen MZ, Teng RJ, Yang MY, Liu HC, Chen RF, Hsu TY, Shaio MF

Author

Ru-Jeng Teng MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Adult
Antioxidants
Apoptosis
Cells, Cultured
DNA Fragmentation
Endotoxemia
Endotoxins
Fetal Blood
Granulocytes
Hematopoiesis
Humans
Infant, Newborn
Interleukin-8
Oxidative Stress
Reactive Oxygen Species
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-403 0f9a74600e4e79798f8fa6f545ea115f3dd948b2