A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis.
Chemokines such as monocyte chemoattractant protein (MCP) -1 and interleukin (IL)-8 are known to be involved in various processes in atherosclerosis such as plaque formation, plaque rupture, and thrombus formation. We investigated whether a new chemokine, Leukotactin (LKN)-1, is involved in atherosclerosis. We tested the expression of LKN-1 by immunohistochemical methods in carotid atherosclerotic plaque specimen. Induction of pro-inflammatory cytokines, transmigration, and tissue factor (TF) expression were tested in THP-1 cells and human peripheral blood monocytes treated with recombinant human LKN-1. Immunohistochemical analyses revealed that expression of LKN-1 occurs in regions of plaques rich in foam cells. In a Boyden chamber assay, THP-1 cells treated with 0.01--10 nM of LKN-1 transmigrated through gelatin coated filters in a dose dependent manner. LKN-1 also induced the transient expression of TNF-alpha, IL-8, and MCP-1 within 15 min of the treatment of the THP-1 cells. When peripheral blood monocytes were treated with LKN-1, expression levels of TF and TF-mediated procoagulating activity were induced in a time- and dose-dependent manner. These results raise the possibility that LKN-1 is another chemokine that is involved in the atherogenesis. LKN-1 may chemoattract immune cells into the plaque, induce pro-inflammatory cytokines, and produce thrombi by inducing TF expression.
Lee
Won-Ha
WH
Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong Kangnam-Ku, Seoul 135-710, South Korea. leewh@pbrc.edu
Kim
Se-Hwa
SH
Jeong
Euy Myoung
EM
Choi
Yoon-Ho
YH
Kim
Dong-Ik
DI
Lee
Byung Boong
BB
Cho
Young S
YS
Kwon
Byoung S
BS
Park
Jeong-Euy
JE
D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000473:pathology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D019742:Chemokines, CC / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012680:Sensitivity and Specificity; D013925:Thromboplastin / Q000187:drug effects* / Q000378:metabolism*
D018932:Chemokine CCL2; D019742:Chemokines, CC; D016209:Interleukin-8; D013925:Thromboplastin