Decrease in scavenger receptor expression in human monocyte-derived macrophages treated with granulocyte macrophage colony-stimulating factor

被引:31
作者
vanderKooij, MA [1 ]
Morand, OH [1 ]
Kempen, HJ [1 ]
vanBerkel, TJC [1 ]
机构
[1] LEIDEN UNIV, LEIDEN AMSTERDAM CTR DRUG RES, DIV BIOPHARMACEUT, 2300 RA LEIDEN, NETHERLANDS
关键词
granulocyte macrophage colony-stimulating factor; atherosclerosis; macrophage; scavenger receptor; cholesterol;
D O I
10.1161/01.ATV.16.1.106
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To determine whether scavenger receptors are susceptible to regulation by granulocyte macrophage colony-stimulating factor (GM-CSF), a macrophage-specific cytokine, human monocytes were differentiated into macrophages in the absence or presence of 20 U/mL GM-CSF. Binding, uptake, and degradation of acetylated LDL (Ac-LDL) and oxidized LDL (Ox-LDL) were measured. Treatment with GM-CSF resulted in a significant twofold to threefold decrease in the number of binding sites for Ac-LDL and Ox-LDL on the surface of macrophages without affecting the affinity of the receptor for these ligands. Competition experiments revealed that two binding sites were responsible for the recognition and uptake of Ac-LDL: one specific for Ac-LDL and one that recognized both Ac LDL and Ox-LDL. No binding site specific for Ox-LDL could be detected in either control or GM-CSF-treated macrophages. Treatment of human monocyte-derived macrophages with GM-CSF resulted in a decrease of the Ac-LDL/Ox-LDL receptor but did not affect the binding Site specific for Ac-LDL. Northern blot analysis showed that mRNA level of both types I and II scavenger receptor were reduced in macrophages differentiated in the presence of GM-CSF. Human macrophages that were differentiated in the presence of GM-CSF accumulated approximate to 50% fewer cholesteryl esters. Taken together, these results indicate that GM-CSF can downregulate both types I and II scavenger receptor in human monocyte-derived macrophages, which might have implications for foam cell formation.
引用
收藏
页码:106 / 114
页数:9
相关论文
共 57 条
[1]   MULTIPLE RECEPTORS FOR MODIFIED LOW-DENSITY LIPOPROTEINS IN MOUSE PERITONEAL-MACROPHAGES - DIFFERENT UPTAKE MECHANISMS FOR ACETYLATED AND OXIDIZED LOW-DENSITY LIPOPROTEINS [J].
ARAI, H ;
KITA, T ;
YOKODE, M ;
NARUMIYA, S ;
KAWAI, C .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 159 (03) :1375-1382
[2]   THE CONTRIBUTION OF THE MACROPHAGE RECEPTOR FOR OXIDIZED LDL TO ITS CELLULAR UPTAKE [J].
AVIRAM, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 179 (01) :359-365
[3]   DEGRADATION OF CATIONIZED LOW-DENSITY LIPOPROTEIN AND REGULATION OF CHOLESTEROL-METABOLISM IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA FIBROBLASTS [J].
BASU, SK ;
GOLDSTEIN, JL ;
ANDERSON, RGW ;
BROWN, MS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1976, 73 (09) :3178-3182
[4]  
BIERMAN EL, 1974, CIRC RES, V35, P136, DOI 10.1161/01.RES.35.1.136
[5]   METABOLISM OF VERY LOW-DENSITY LIPOPROTEIN PROTEINS .1. PRELIMINARY IN-VITRO AND IN-VIVO OBSERVATIONS [J].
BILHEIMER, DW ;
LEVY, RI ;
EISENBERG, S .
BIOCHIMICA ET BIOPHYSICA ACTA, 1972, 260 (02) :212-+
[6]  
BOTTALICO LA, 1991, J BIOL CHEM, V266, P22866
[7]  
BOYUM A, 1968, SCAND J CLIN LAB INV, VS 21, P77
[8]   A RECEPTOR-MEDIATED PATHWAY FOR CHOLESTEROL HOMEOSTASIS [J].
BROWN, MS ;
GOLDSTEIN, JL .
SCIENCE, 1986, 232 (4746) :34-47
[9]   LIPOPROTEIN METABOLISM IN THE MACROPHAGE - IMPLICATIONS FOR CHOLESTEROL DEPOSITION IN ATHEROSCLEROSIS [J].
BROWN, MS ;
GOLDSTEIN, JL .
ANNUAL REVIEW OF BIOCHEMISTRY, 1983, 52 :223-261
[10]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159