title: LOX-1 in macrophage migration in response to ox-LDL and the involvement of calpains.
abstract: Previous studies have shown that oxidized low-density lipoprotein (ox-LDL) inhibits macrophage migration, but the precise mechanisms remain unclear. Lectin-like ox-LDL receptor-1 (LOX-1) is a scavenger receptor that is expressed in macrophages and binds ox-LDL. Calpains, a family of calcium-dependent proteases, influence several aspects of cell migration. In this study, we investigated the role of LOX-1 in macrophage migration in response to ox-LDL and the involvement of calpains in this process. Peritoneal macrophages from wild type C57BL/6 mice were exposed to different concentrations of ox-LDL (1-20 μg/mL), and expression of LOX-1 and calpain-1 and -2, cell migration and intracellular calcium (Ca(2+)in) were measured. Our results showed that ox-LDL stimulated LOX-1 and calpain-2 expression, and inhibited calpain-1 expression in a dose- and time-dependent manner. Further, ox-LDL inhibited macrophage migration and increased Ca(2+)in concentration in macrophages. To further elucidate the role of LOX-1 in ox-LDL-impaired macrophage migration, we isolated peritoneal macrophages from LOX-1 knockout mice, and treated them with ox-LDL. Interestingly, calpain-1 expression was much higher, and calpain-2 expression was lower in LOX-1 knockout macrophages than in wild-type macrophages following exposure to ox-LDL. LOX-1 deletion significantly improved macrophage migration and decreased Ca(2+)in concentration. These data indicate that LOX-1 is, at least in part, responsible for the inhibitory effect of ox-LDL on macrophage migration and this process involves calpain-1 and -2.
authors.affiliation: Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, China; Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Juntang
authors.initials: J
authors.lastname: Lin
authors.affiliation: Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Central Arkansas Veterans Healthcare System, and the Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: MehtaJL@UAMS.edu.
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D002232:Carbocyanines; D002465:Cell Movement / Q000187:drug effects; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051127:Scavenger Receptors, Class E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C582073:1,1'-dioleyl-3,3,3',3'-tetramethylindocarbocyanine; D002232:Carbocyanines; D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL; C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D002154:Calpain; C112682:Capn1 protein, mouse; C570925:Capn2 protein, mouse; D002118:Calcium
keywords: Calcium; Calpains; Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1); Macrophage migration; Oxidized low-density lipoprotein