Lectin-like oxidized LDL receptor 1 is involved in CRP-mediated complement activation

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• C-reactive protein (CRP) is a risk factor for mortality in ischemic heart disease, independent of LDL cholesterol.
• Lectin-like oxidized LDL receptor 1 (LOX-1) is implicated in endothelial dysfunction and myocardial injury.
• Previous work showed CRP increases vascular permeability by binding to LOX-1.

Purpose of the Study:

• To investigate the role of LOX-1 in C-reactive protein (CRP)-induced complement activation.
• To examine this interaction in a hypertensive rat model.

Main Methods:

• Utilized a cultured LOX-1-expressing cell line (hLOX-1-CHO) and native CHO cells.
• Performed complement activation assays with and without C1q depletion.
• Used immobilized recombinant LOX-1 and CRP with serum.
• Administered CRP intradermally to hypertensive rats (SHRSP).
• Assessed complement activation via C3d deposition and leukocyte infiltration.
• Investigated the effect of anti-LOX-1 antibody in vivo.

Main Results:

• CRP induced complement activation in LOX-1-expressing cells but not in native cells.
• C1q depletion abolished CRP-induced complement activation.
• CRP activated the classical complement pathway via LOX-1 in a calcium-dependent manner, with binding influenced by phosphocholine.
• In hypertensive rats, CRP injection led to complement activation and leukocyte infiltration.
• Anti-LOX-1 antibody significantly reduced these effects.

Conclusions:

• Lectin-like oxidized LDL receptor 1 (LOX-1) plays a role in C-reactive protein (CRP)-induced complement activation.
• LOX-1 may direct the localization of CRP-mediated complement activation and subsequent inflammation.