Gene expression profiling of apoptosis regulators in patients with sepsis.
BACKGROUND
Sepsis is associated with a dysregulation of apoptosis in immune cells, which has been implicated in both immunosuppression and multiple organ failure. We describe the expression profiles of genes encoding key regulators of apoptosis in highly purified monocytes, granulocytes and CD4+ T lymphocytes.


METHODS
Sixteen patients with sepsis were recruited from the intensive care unit and were compared with 24 healthy controls. RNA was isolated from highly purified monocyte, granulocyte and CD4+ T-lymphocyte populations. Gene expression profiles were determined using multiplex ligation-dependent probe amplification for the simultaneous detection of 30 pro- and anti-apoptotic target genes.


RESULTS
Relative to healthy controls, patients with sepsis showed increased transcription of both pro- and anti-apoptotic genes in peripheral blood leukocytes. Specific monocyte, granulocyte and CD4+ T-lymphocyte mRNA profiles were identified. Anti-apoptotic profiles were found in monocytes and granulocytes, while CD4+ T lymphocytes displayed a foremost pro-apoptotic mRNA profile.


CONCLUSIONS
These data indicate that in patients with sepsis, the alterations in apoptosis of circulating leukocytes occur in a cell-specific manner.
Hoogerwerf
Jacobien J
JJ
Centers for Infection and Immunity Amsterdam, and Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. j.j.hoogerwerf@amc.uva.nl
van Zoelen
Marieke A
MA
Wiersinga
W Joost
WJ
van 't Veer
Cornelis
C
de Vos
Alex F
AF
de Boer
Anita
A
Schultz
Marcus J
MJ
Hooibrink
Berend
B
de Jonge
Evert
E
van der Poll
Tom
T
D000368:Aged; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000097:blood* / Q000276:immunology*
D011506:Proteins; D012333:RNA, Messenger