Higher spontaneous and TNFalpha-induced apoptosis of neonatal blood granulocytes.
Granulocytes play an important role in inflammatory diseases. Neonates tend to develop granulocytopenia under sepsis and stress. It remains unclear whether apoptosis of neonatal granulocytes is different from that of adult granulocytes. In this study, we analyzed the discrepancy of granulocyte apoptosis between cord blood (CB) and adult blood (AB). We found that spontaneous and tumor necrosis factor-alpha (TNFalpha)-induced granulocyte apoptosis as determined by phosphatidylserine expression and DNA fragmentation were more prominent in CB granulocytes than AB granulocytes. CD95 ligand and TNFalpha levels were significantly higher in CB than in AB (p = 0.001 and p < 0.001, respectively). TNF receptor-2 and CD95 expression on CB granulocytes were not different from those on AB granulocytes. However, the TNF receptor-1 (TNFR1) expression was lower on CB granulocytes than that on AB granulocytes (69.98 +/- 7.32 versus 89.04 +/- 3.73%, p = 0.029). This decrease of TNFR1 expression on neonatal granulocytes might be related to a higher plasma TNFalpha level associated with an intrinsic defect on the dynamic change of membrane TNFR1 expression in neonatal granulocytes. The expression of anti-apoptotic molecule Bcl-2 in neonatal granulocytes was also lower than that in adult granulocytes (4.64 +/- 0.51 versus 7.24 +/- 1.17 unit/mg protein, p = 0.032). Moreover, another anti-apoptotic signal, nuclear factor-kappaB nuclear translocation, was also lower in CB than AB granulocytes. Results from this study suggest that higher plasma death ligands associated with lower anti-apoptotic molecules in granulocytes may act an important role in triggering neonatal granulocyte apoptosis.
Liu
Chieh-An
CA
Departments of Neonatology and Clinical Immunology, Chang Gung Children Hospital at Kaohsiung, Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung, Taiwan 833.
Wang
Chih-Lu
CL
Wang
Feng-Sheng
FS
Huang
Hsin-Chun
HC
Chuang
Hau
H
Chen
Ron-Fu
RF
Tai
Fang-Yu
FY
Yang
Kuender D
KD
D021581:Active Transport, Cell Nucleus; D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D053938:DNA Fragmentation; D015536:Down-Regulation; D005312:Fetal Blood / Q000378:metabolism; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D007249:Inflammation; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000096:biosynthesis / Q000737:chemistry
D008024:Ligands; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor