期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：9
页码：6298-6303
DOI：10.1073/pnas.092327399
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The ATP-binding cassette transporter 1 (ABCA1) has recently been identified as a key regulator of high-density lipoprotein (HDL) metabolism, which is defective in familial HDL-deficiency syndromes such as Tangier disease. ABCA1 functions as a facilitator of cellular cholesterol and phospholipid efflux, and its expression is induced during cholesterol uptake in macrophages. To assess the role of macrophage ABCA1 in atherosclerosis, we generated low-density lipoprotein (LDL) receptor knockout (LDLr-/-) mice that are selectively deficient in leukocyte ABCA1 (ABCA1-/-) by using bone marrow transfer (ABCA1-/- [->] LDLr-/-). Here we demonstrate that ABCA1-/- [->] LDLr-/- chimeras develop significantly larger and more advanced atherosclerotic lesions compared with chimeric LDLr-/- mice with functional ABCA1 in hematopoietic cells. Targeted disruption of leukocyte ABCA1 function did not affect plasma HDL cholesterol levels. The amount of macrophages in liver and spleen and peripheral blood leukocyte counts is increased in the ABCA1-/- [->] LDLr-/- chimeras. Our results provide evidence that leukocyte ABCA1 plays a critical role in the protection against atherosclerosis, and we identify ABCA1 as a leukocyte factor that controls the recruitment of inflammatory cells.
