title: Lectin-like oxidized LDL receptor 1 is involved in CRP-mediated complement activation.
abstract: BACKGROUND
  C-reactive protein (CRP) is purported to be a risk factor that acts independently of LDL cholesterol in predicting all-cause mortality in patients with ischemic heart disease. Lectin-like oxidized LDL receptor 1 (LOX-1) impairs endothelial function and exacerbates myocardial injury. We recently demonstrated that CRP increased vascular permeability through direct binding to LOX-1. Here we examined, using a hypertensive rat model, whether LOX-1 is involved in CRP-induced complement activation.
  
  
  RESULTS
  In the cultured LOX-1-expressing cell line hLOX-1-CHO, CRP increased complement activation, but did not do so in native CHO cells. Depleting C1q from serum abolished CRP-induced complement activation. Incubation of CRP with serum on immobilized recombinant LOX-1 similarly showed that CRP activated C1q-requiring classical complement pathway in a LOX-1-dependent manner. Interestingly, the interaction between CRP and LOX-1 was dependent on Ca²⁺ ion and competed with phosphocholine, suggesting that LOX-1 bound to the B-face of CRP with a phosphocholine-binding domain. This was in contrast to Fcγ receptors, to which CRP bound in A-face with complement-binding domain. In vivo, intradermal injection of CRP to hypertensive SHRSP rats induced complement activation detected by C3d deposition and leukocyte infiltration around the injected area. Anti-LOX-1 antibody reduced the extent of complement activation and leukocyte infiltration.
  
  
  CONCLUSIONS
  LOX-1 appears to be involved in CRP-induced complement activation, and thus may serve to locate the site of CRP-induced complement activation and inflammation.
authors.affiliation: Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Saburo
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Akemi
authors.initials: A
authors.lastname: Kakino
authors.forename: Shin
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Yoshimoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002097:C-Reactive Protein / Q000494:pharmacology / Q000502:physiology*; D016466:CHO Cells; D002474:Cell-Free System; D003167:Complement Activation; D015922:Complement C1q / Q000378:metabolism; D015933:Complement C3d / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D055767:Immobilized Proteins; D008297:Male; D020556:Neutrophil Infiltration; D010767:Phosphorylcholine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology; D051127:Scavenger Receptors, Class E / Q000276:immunology / Q000502:physiology*; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D055767:Immobilized Proteins; D011994:Recombinant Proteins; D051127:Scavenger Receptors, Class E; D010767:Phosphorylcholine; D015922:Complement C1q; D015933:Complement C3d; D002097:C-Reactive Protein