Contribution of monocytes Siglec-1 in stimulating T cells proliferation and activation in atherosclerosis.
OBJECTIVE
Atherosclerosis (AS) is widely accepted as an inflammatory disease and monocytes are particularly important in inflammatory immune responses. As an important biomarker of monocytes activation, Siglec-1 is highly expressed on circulating monocytes and atherosclerotic plaques of coronary artery disease (CAD) patients, but the exact role of Siglec-1 has not been elucidated.


METHODS
M-CSF, INF-α, IFN-γ, TNF-α and ox-LDL alone or in combination were used to stimulate Siglec-1 expression on monocytes, whereas small interfering RNA (si-RNA) or blocking antibody was used to down-regulate Siglec-1. Meanwhile, the role of Siglec-1 in chemokines secretion was determined. Then monocytes from CAD patients or healthy controls were cocultured with CD4+ or CD8+ T cells from a third healthy individual, and lymphocyte proliferation and activation were determined.


RESULTS
All the stimuluses could enhance Siglec-1 expression on monocytes in a dose-dependent manner, and M-CSF could synergistically stimulate Siglec-1 expression with ox-LDL. Moreover, the secretion of MCP-1, MIP-1α and MIP-2 were enhanced when Siglec-1 was up-regulated and down to normal level when Siglec-1 was blocked. More importantly, increased Siglec-1 expression on monocytes was related to the increased T cell proliferation and pro-inflammatory cytokines secretion in CAD patients. However, down-regulation of Siglec-1 could attenuate proliferation and activation of cocultured CD4+ and CD8+ T cells.


CONCLUSIONS
Siglec-1 can promote chemokines and pro-inflammatory cytokines secretion and influence the inflammatory process of AS.
Department of Laboratory Medicine, Chengdu Military General Hospital, Chengdu, China. xys10@163.com
Yi-song
YS
Xiong
Ai-lin
AL
Wu
Qiu-shui
QS
Lin
Juan
J
Yu
Chang
C
Li
Lin
L
Zhu
Ren-qian
RQ
Zhong
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology; D049109:Cell Proliferation; D003324:Coronary Artery Disease / Q000276:immunology; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D063267:Sialic Acid Binding Ig-like Lectin 1