Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli.
BACKGROUND
Neonates show sustained inflammation after a bacterial infection, which is associated with inflammatory diseases like bronchopulmonary dysplasia or periventricular leucomalacia. Physiologically, inflammation is terminated early after the removal of the invading pathogens by phagocytosis-induced cell death (PICD) of immune effector cells. Earlier results showed reduced PICD in neonatal monocytes. The underlying molecular mechanisms are unknown. We hypothesize that the reduced PICD in neonatal monocytes is regulated through the proteins of the B-cell lymphoma 2 (Bcl-2) protein family.


METHODS
mRNA and protein expression of Bcl-2 family proteins in cord blood and adult peripheral blood monocytes infected with Escherichia coli were analyzed by quantitative real-time PCR and flow cytometry and cytochrome c release by fluorescence microscopy.


RESULTS
mRNA expression of antiapopototic Bcl-xL was upregulated in cord blood monocytes (CBMO), whereas proapoptotic Bim tended to be higher in peripheral blood monocytes (PBMO). Upon infection, Bax was more strongly expressed in PBMO compared with CBMO. The pro/antiapoptotic balance was skewed toward survival in CBMO and apoptosis in PBMO. Cytochome c release into the cytosol was enhanced in PBMO compared with CBMO.


CONCLUSIONS
Bcl-2 proteins are involved in reduced PICD in neonatal monocytes. These findings are another step toward the understanding of sustained inflammation in neonates.
Department of Neonatology, University of Tuebingen, Tuebingen, Germany.
Anja
A
Leiber
Department of Neonatology, University of Tuebingen, Tuebingen, Germany.
Benjamin
B
Graf
Department of Neonatology, University of Tuebingen, Tuebingen, Germany.
Bärbel
B
Spring
Institute for Cell Biology, University of Essen, Essen, Germany.
Justine
J
Rudner
Department of Neonatology, University of Tuebingen, Tuebingen, Germany.
Natascha
N
Köstlin
Department of Neonatology, University of Aachen, Aachen, Germany.
Thorsten W
TW
Orlikowsky
Department of Neonatology, University of Tuebingen, Tuebingen, Germany.
Christian F
CF
Poets
Department of Neonatology, University of Tuebingen, Tuebingen, Germany.
Christian
C
Gille
D000328:Adult; D000704:Analysis of Variance; D017209:Apoptosis / Q000276:immunology*; D045304:Cytochromes c / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
D017931:DNA Primers; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c