The early immunological response to acute ischemic stroke: differential gene expression in subpopulations of mononuclear cells.
Peripheral blood mononuclear cells (PBMCs), i.e. lymphocytes, monocytes and macrophages are key players in the development of innate and adaptive immune responses. However, little is known about their properties in patients with acute stroke.


METHODS
We presently characterized the early time course of PBMC subpopulations in 19 patients with acute ischemic stroke and symptom onset below 6 h compared to 19 age-matched healthy subjects. Immediately after acute ischemic stroke, as well as 1 and 3 days thereafter, PBMC subpopulations (cluster of differentiation [CD]3+, CD14+, CD19+, CD68+) were isolated by magnetic bead system and the expression of proinflammatory (CD40, tumor necrosis factor-alpha [TNFalpha]), proapoptotic (caspase-3 [CPP32], poly(ADP-ribose) polymerase [PARP]) and adhesion relevant (CD38) genes was measured by quantitative polymerase chain reaction (PCR). Furthermore, besides routine parameters, plasma levels of oxidized low-density lipoproteins (oxLDL) were studied.


RESULTS
In comparison to healthy subjects, patients revealed (i) twofold elevated plasma oxLDL concentrations, (ii) decreased (15%) blood cholesterol levels, and (iii) a 40% decrease in total number of lymphocytes. Furthermore, the majority of PBMC subpopulations revealed an increased expression of proinflammatory, proapoptotic or adhesion-relevant genes. Significant positive correlations were observed between expression of most of these genes in PBMCs and individual plasma oxLDL concentrations.


CONCLUSIONS
Elevated expression of proinflammatory, proapoptotic and adhesion genes in subsets of PBMCs after ischemic stroke may contribute to an immunodepressive syndrome, possibly due to increased plasma oxLDL levels.
Kassner
S S
SS
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Kollmar
R
R
Bonaterra
G A
GA
Hildebrandt
W
W
Schwab
S
S
Kinscherf
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000276:immunology*; D016022:Case-Control Studies; D002452:Cell Count; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood*; D016131:Lymphocyte Subsets; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D012016:Reference Values; D018709:Statistics, Nonparametric; D020521:Stroke / Q000150:complications / Q000276:immunology*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein