Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study.
Ischemic brain and peripheral white blood cells release cytokines, chemokines and other molecules that activate the peripheral white blood cells after stroke. To assess gene expression in these peripheral white blood cells, whole blood was examined using oligonucleotide microarrays in 15 patients at 2.4+/-0.5, 5 and 24 h after onset of ischemic stroke and compared with control blood samples. The 2.4-h blood samples were drawn before patients were treated either with tissue-type plasminogen activator (tPA) alone or with tPA plus Eptifibatide (the Combination approach to Lysis utilizing Eptifibatide And Recombinant tPA trial). Most genes induced in whole blood at 2 to 3 h were also induced at 5 and 24 h. Separate studies showed that the genes induced at 2 to 24 h after stroke were expressed mainly by polymorphonuclear leukocytes and to a lesser degree by monocytes. These genes included: matrix metalloproteinase 9; S100 calcium-binding proteins P, A12 and A9; coagulation factor V; arginase I; carbonic anhydrase IV; lymphocyte antigen 96 (cluster of differentiation (CD)96); monocarboxylic acid transporter (6); ets-2 (erythroblastosis virus E26 oncogene homolog 2); homeobox gene Hox 1.11; cytoskeleton-associated protein 4; N-formylpeptide receptor; ribonuclease-2; N-acetylneuraminate pyruvate lyase; BCL6; glycogen phosphorylase. The fold change of these genes varied from 1.6 to 6.8 and these 18 genes correctly classified 10/15 patients at 2.4 h, 13/15 patients at 5 h and 15/15 patients at 24 h after stroke. These data provide insights into the inflammatory responses after stroke in humans, and should be helpful in diagnosis, understanding etiology and pathogenesis, and guiding acute treatment and development of new treatments for stroke.
Tang
Yang
Y
MIND Institute and Department of Neurology, University of California at Davis, Sacramento, California 95817, USA.
Xu
Huichun
H
Du
XinLi
X
Lit
Lisa
L
Walker
Wynn
W
Lu
Aigang
A
Ran
Ruiqiong
R
Gregg
Jeffrey P
JP
Reilly
Melinda
M
Pancioli
Art
A
Khoury
Jane C
JC
Sauerbeck
Laura R
LR
Carrozzella
Janice A
JA
Spilker
Judith
J
Clark
Joseph
J
Wagner
Kenneth R
KR
Jauch
Edward C
EC
Chang
Dongwoo J
DJ
Verro
Piero
P
Broderick
Joseph P
JP
Sharp
Frank R
FR
D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D020521:Stroke / Q000097:blood* / Q000188:drug therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D010959:Tissue Plasminogen Activator; D000077542:Eptifibatide