Cellular actors, Toll-like receptors, and local cytokine profile in acute coronary syndromes.
OBJECTIVE
Inflammation plays a key role in acute coronary syndromes (ACS). Toll-like receptors (TLR) on leucocytes mediate inflammation and immune responses. We characterized leucocytes and TLR expression within coronary thrombi and compared cytokine levels from the site of coronary occlusion with aortic blood (AB) in ACS patients.


RESULTS
In 18 ACS patients, thrombi were collected by aspiration during primary percutaneous coronary intervention. Thrombi and AB from these patients as well as AB from 10 age-matched controls without coronary artery disease were assessed by FACS analysis for cellular distribution and TLR expression. For further discrimination of ACS specificity, seven non-coronary intravascular thrombi and eight thrombi generated in vitro were analysed. In 17 additional patients, cytokine levels were determined in blood samples from the site of coronary occlusion under distal occlusion and compared with AB. In coronary thrombi from ACS, the percentage of monocytes related to the total leucocyte count was greater than in AB (47 vs. 20%, P = 0.0002). In thrombi, TLR-4 and TLR-2 were overexpressed on CD14-labelled monocytes, and TLR-2 was increased on CD66b-labelled granulocytes, in comparison with leucocytes in AB. In contrast, in vitro and non-coronary thrombi exhibited no overexpression of TLR-4. Local blood samples taken under distal occlusion revealed elevated concentrations of chemokines (IL-8, MCP-1, eotaxin, MIP-1alpha, and IP-10) and cytokines (IL-1ra, IL-6, IL-7, IL-12, IL-17, IFN-alpha, and granulocyte-macrophage colony-stimulating factor) regulating both innate and adaptive immunity (all P < 0.05).


CONCLUSIONS
In ACS patients, monocytes accumulate within thrombi and specifically overexpress TLR-4. Together with the local expression patterns of chemokines and cytokines, the increase of TLR-4 reflects a concerted activation of this inflammatory pathway at the site of coronary occlusion in ACS.
Wyss
Christophe A
CA
Department of Cardiology, Cardiovascular Center, University Hospital, Rämistrasse 100, CH - 8091 Zurich, Switzerland.
Neidhart
Michel
M
Altwegg
Lukas
L
Spanaus
Katharina S
KS
Yonekawa
Keiko
K
Wischnewsky
Manfred B
MB
Corti
Roberto
R
Kucher
Nils
N
Roffi
Marco
M
Eberli
Franz R
FR
Amann-Vesti
Beatrice
B
Gay
Steffen
S
von Eckardstein
Arnold
A
Lüscher
Thomas F
TF
Maier
Willibald
W
D054058:Acute Coronary Syndrome / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D001011:Aorta; D016022:Case-Control Studies; D054059:Coronary Occlusion / Q000378:metabolism*; D003328:Coronary Thrombosis / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012307:Risk Factors; D051193:Toll-Like Receptors / Q000378:metabolism*
D016207:Cytokines; D051193:Toll-Like Receptors