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.

METHODS AND 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: Yoshiko Fujita, Saburo Yamaguchi, Akemi Kakino, Shin Iwamoto, Ryo Yoshimoto, Tatsuya Sawamura
• Journal: Clinical chemistry (Clin Chem) Vol. 57 Issue 10 Pg. 1398-405 (Oct 2011) ISSN: 1530-8561 [Electronic] England
• PMID: 21821723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Immobilized Proteins
• Recombinant Proteins
• Scavenger Receptors, Class E
• Phosphorylcholine
• Complement C1q
• Complement C3d
• C-Reactive Protein

Topics

• Animals
• Antibodies (pharmacology)
• C-Reactive Protein (pharmacology, physiology)
• CHO Cells
• Cell-Free System
• Complement Activation
• Complement C1q (metabolism)
• Complement C3d (metabolism)
• Cricetinae
• Cricetulus
• Humans
• Immobilized Proteins
• Male
• Neutrophil Infiltration
• Phosphorylcholine (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Recombinant Proteins (pharmacology)
• Scavenger Receptors, Class E (immunology, physiology)
• Skin (blood supply, drug effects, immunology)