High-density lipoproteins inhibit fibrinogen binding on adenosine diphosphate-activated monocytes.
High levels of fibrinogen and low levels of high-density lipoprotein (HDL) cholesterol were reported to be risk factors for coronary heart disease. CD11b/CD18, a fibrinogen-binding protein, is expressed on the surface of monocytes, which play a crucial role in the formation of atherosclerotic lesions. In the present study, we investigate the effects of antibodies against CD11b and CD18, as well as HDL3 and low-density lipoprotein (LDL) cholesterol on fibrinogen binding on monocytes. We find that binding of fibrinogen on monocytes activated with adenosine diphosphate (ADP) was reduced to 66.0+/-8.3% (mean +/- SD) in the presence of anti-CD11b antibodies (12.5 microg/ml; P < or = 0.02) and to 54.5+/-4.9% in the presence of anti-CD18 antibodies (20 microg/ml; P < or = 0.01), respectively. Fibrinogen binding on Cytochalasin-B-activated monocytes was reduced to 79.8+/-6.0% in the presence of anti-CD18 (20 microg/ml; P < or = 0.05). Incubation of ADP-activated monocytes with HDL3 (0.5 g/l) led to a lowering of fibrinogen binding to 65.0+/-6.6% (P < or = 0.05). No effect of HDL3 on fibrinogen binding was seen on Cytochalasin-B-activated monocytes. A slight, non-significant stimulatory effect of LDL on fibrinogen binding on ADP-activated but not on Cytochalasin-B-activated monocytes was additionally observed. Neither incubation with HDL3 or with LDL had a significant influence on ADP-activated cellular binding of anti-CD11b or anti-CD18 antibodies. The inhibition of fibrinogen binding on monocytes in the presence of HDL3 is a major new finding of this study. Since inhibition of fibrinogen binding in the presence of HDL might impair both monocyte recruitment to the arterial wall and foam cells formation, our findings suggests a novel mechanism by which HDL may prevent development of arteriosclerosis.
Neufeld
M
M
Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, Germany.
Nofer
J R
JR
Becker
P
P
Langer
C
C
Assmann
G
G
Junker
R
R
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000906:Antibodies; D018821:CD18 Antigens / Q000276:immunology; D008076:Cholesterol, HDL / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects
D000906:Antibodies; D018821:CD18 Antigens; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D000244:Adenosine Diphosphate; D005340:Fibrinogen