Lysophosphatidic acid-induced oxidized low-density lipoprotein uptake is class A scavenger receptor-dependent in macrophages.
Lysophosphatidic acid (LPA) is a low-molecular-weight lysophospholipid enriched in platelets and mildly oxidized low-density lipoprotein (OxLDL). It is suggested that LPA is involved in atherosclerosis, and our previous studies showed that LPA regulates inflammation in multiple cell types. The main aim of this study was to investigate the effects of LPA on the uptake of OxLDL by mouse J774A.1 macrophages. We observed that LPA upregulated fluorescence-labeled DiI-OxLDL uptake in J774A.1 cells. Meanwhile, expression of the class A scavenger receptor (SR-A), a receptor for modified LDL, was also enhanced. Furthermore, pertussis toxin (PTx) or Ki16425 significantly abolished LPA's effects, indicating that G(i) and LPA(3) are involved in OxLDL uptake and SR-A expression. Of most importance, the LPA-induced OxLDL uptake could be inhibited when cells were incubated with a functional blocking antibody of SR-A. Our results suggest that LPA-enhanced OxLDL uptake is mediated via LPA(3)-G(i) activation and subsequent SR-A expression.
Chang
Chi-Lun
CL
Institute of Zoology, National Taiwan University, Taipei, Taiwan, ROC.
Hsu
Hsien-Yeh
HY
Lin
Hong-Yu
HY
Chiang
Wenchang
W
Lee
Hsinyu
H
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
D000906:Antibodies; D008077:Lipoproteins, LDL; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; C099252:oxidized low density lipoprotein; C032881:lysophosphatidic acid