Upregulation of CD40-CD40 ligand (CD154) in patients with acute cerebral ischemia.
OBJECTIVE
Inflammation and hypercoagulability contribute to the development of acute cerebral ischemia. Both can be mediated by the CD40 system. This study investigated whether the CD40 system and related mediators are upregulated in patients with transient ischemic attack (TIA) or stroke.


METHODS
Seventeen patients with TIA, 60 patients with complete stroke, and 15 control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 on monocytes during and 3 months after acute cerebral ischemia by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated.


RESULTS
Our main findings are as follows: (1) patients with acute cerebral ischemia showed a significant increase of CD154 on platelets and CD40 on monocytes compared with controls; (2) plasma levels of soluble CD154 were significantly higher in these patients; (3) these patients had significantly higher numbers of prothrombotic platelet-monocyte aggregates; (4) the chemoattractant MCP-1 was significantly elevated in cerebral ischemia; and (5) at 3 months' follow-up, upregulation of CD154 still persisted in patients with previous acute cerebral ischemia.


CONCLUSIONS
Patients with acute cerebral ischemia show upregulation of the CD40 system, which might contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.
Garlichs
C D
CD
Medical Clinic II, Friedrich-Alexander-University Erlangen-Nuremberg, David-Morgenstern-Weg 14, 91056 Erlangen, Germany. Christoph.Garlichs@rzmail.uni-erlangen.de
Kozina
S
S
Fateh-Moghadam
S
S
Handschu
R
R
Tomandl
B
B
Stumpf
C
C
Eskafi
S
S
Raaz
D
D
Schmeisser
A
A
Yilmaz
A
A
Ludwig
J
J
Neundörfer
B
B
Daniel
W G
WG
D000208:Acute Disease; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000097:blood / Q000378:metabolism*; D002452:Cell Count; D018932:Chemokine CCL2 / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012016:Reference Values; D015854:Up-Regulation
D015415:Biomarkers; D019013:CD40 Antigens; D018932:Chemokine CCL2; D019007:P-Selectin; D015375:Receptors, Interleukin-2; D023201:CD40 Ligand; D002097:C-Reactive Protein