UPTAKE OF EXOGENOUS FREE-CHOLESTEROL INDUCES UP-REGULATION OF TISSUE FACTOR EXPRESSION IN HUMAN MONOCYTE-DERIVED MACROPHAGES

被引:85
作者
LESNIK, P [1 ]
ROUIS, M [1 ]
SKARLATOS, S [1 ]
KRUTH, HS [1 ]
CHAPMAN, MJ [1 ]
机构
[1] NHLBI,EXPTL ATHEROSCLEROSIS SECT,BETHESDA,MD 20892
关键词
THROMBOSIS; ATHEROSCLEROSIS;
D O I
10.1073/pnas.89.21.10370
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Lipid-laden macrophages present as foam cells may contribute to the hyperthrombotic state of human atherosclerotic lesions by the production of tissue factor (TF). We investigated the effect of exogenous nonlipoprotein cholesterol on the expression of TF by human monocyte-derived macrophages in culture. Nonlipoprotein cholesterol at 50 mug/ml increased TF activity 4-fold; TF induction was dose- and time-dependent. Expression of TF activity was positively correlated with the free cholesterol content of monocyte-derived macrophages, was increased upon inhibition of cholesterol esterification, and reflected de novo synthesis of TF protein. TF expression in cholesterol-loaded macrophages remained sensitive to stimulation (almost-equal-to 12-fold) by bacterial lipopolysaccharide, indicating that intracellular free cholesterol and lipopolysaccharide act by distinct mechanisms in inducing TF procoagulant activity. Our results suggest that loading human monocyte-derived macrophages with free cholesterol induces upregulation of TF expression, thereby contributing to thrombus formation at sites of plaque rupture.
引用
收藏
页码:10370 / 10374
页数:5
相关论文
共 26 条
[1]   INITIATION OF COAGULATION BY TISSUE FACTOR [J].
BACH, RR .
CRC CRITICAL REVIEWS IN BIOCHEMISTRY, 1988, 23 (04) :339-368
[2]   RECOMBINANT TUMOR-NECROSIS-FACTOR INDUCES PROCOAGULANT ACTIVITY IN CULTURED HUMAN VASCULAR ENDOTHELIUM - CHARACTERIZATION AND COMPARISON WITH THE ACTIONS OF INTERLEUKIN-1 [J].
BEVILACQUA, MP ;
POBER, JS ;
MAJEAU, GR ;
FIERS, W ;
COTRAN, RS ;
GIMBRONE, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (12) :4533-4537
[3]   FLUORESCENCE STUDIES OF BINDING OF POLYENE ANTIBIOTICS FILIPIN III, AMPHOTERICIN-B, NYSTATIN, AND LAGOSIN TO CHOLESTEROL [J].
BITTMAN, R ;
FISCHKOF.A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1972, 69 (12) :3795-3799
[4]  
BRAND K, 1990, ARTERIOSCLEROSIS, V10, pA760
[5]   TISSUE FACTOR MESSENGER-RNA IN THP-1 MONOCYTIC CELLS IS REGULATED AT BOTH TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL LEVELS IN RESPONSE TO LIPOPOLYSACCHARIDE [J].
BRAND, K ;
FOWLER, BJ ;
EDGINGTON, TS ;
MACKMAN, N .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (09) :4732-4738
[6]  
CHAPMAN MJ, 1988, J LIPID RES, V29, P442
[7]  
CONKLING PR, 1988, BLOOD, V72, P128
[8]  
DRAKE TA, 1989, AM J PATHOL, V134, P1087
[9]  
DRAKE TA, 1991, AM J PATHOL, V138, P601
[10]   REGULATION OF TISSUE FACTOR GENE-EXPRESSION IN THE MONOCYTE PROCOAGULANT RESPONSE TO ENDOTOXIN [J].
GREGORY, SA ;
MORRISSEY, JH ;
EDGINGTON, TS .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (06) :2752-2755