Antiphospholipid antibodies induce monocyte chemoattractant protein-1 in endothelial cells.
The presence of antiphospholipid Ab is associated with increased risk of thrombosis. The monocyte-endothelial cell interaction has been suggested to play a key role at the site of vascular injury during thrombosis. Therefore, we tested the effect of anticardiolipin Abs (aCL) on the production of monocyte chemoattractant protein-1 (MCP-1) in HUVEC. We found that monoclonal aCL as well as IgG fractions from patients with antiphospholipid syndrome (APS-IgG) could induce the production of MCP-1 in HUVEC. The ability of IgG aCL to induce MCP-1 production could be abrogated by preabsorption with cardiolipin liposomes. Simultaneous addition of either monoclonal aCL or APS-IgG with IL-1beta resulted in synergistic increase in MCP-1 production, whereas the addition of control IgG lacking aCL activity did not alter IL-1beta-induced levels of MCP-1. MCP-1 mRNA expression was also up-regulated when HUVEC were incubated with either APS-IgG or monoclonal aCL, and down-regulated by the treatment of dexamethasone. In addition, we found that serum levels of MCP-1 in 76 systemic lupus erythematosus patients correlated well with the titers of IgG aCL. Collectively, these results indicate that aCL could promote endothelial cell-monocyte cross-talk by enhancing the endothelial production of MCP-1, thereby shifting the hemostatic balance toward the prothrombotic state of APS.
Cho
Chul-Soo
CS
Department of Medicine, Division of Rheumatology, Center for Rheumatic Diseases, Kangnam St. Mary's Hospital, Catholic University of Korea, Seoul, Korea. chocs@cmc.cuk.ac.kr
Cho
Mi-La
ML
Chen
Pojen P
PP
Min
So-Youn
SY
Hwang
Sue-Yun
SY
Park
Kyung-Soo
KS
Kim
Wan-Uk
WU
Min
Do-June
DJ
Min
Jun-Ki
JK
Park
Sung-Hwan
SH
Kim
Ho-Youn
HY
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D053482:beta 2-Glycoprotein I
D000276:Adjuvants, Immunologic; D017153:Antibodies, Anticardiolipin; D018932:Chemokine CCL2; D006023:Glycoproteins; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D012333:RNA, Messenger; D053482:beta 2-Glycoprotein I; D003907:Dexamethasone