C-reactive protein uptake by macrophage cell line via class-A scavenger receptor.

C-reactive protein (CRP) increases in response to inflammation and is purported to be a risk factor for atherogenesis. We recently demonstrated that a scavenger receptor, lectin-like oxidized LDL receptor (LOX-1), is a receptor for CRP. In light of the overlapping ligand spectrum of scavenger receptors such as modified LDL, bacteria, and advanced glycation end products, we examined whether other scavenger receptors recognize CRP. We analyzed the uptake of fluorescently labeled CRP in COS-7 cells expressing a series of scavenger receptors and in a monocytic cell line, THP-1, differentiated into macrophage with phorbol 12-myristate 13-acetate (PMA). We applied small interfering RNA (siRNA) against class-A scavenger receptor (SR-A) to THP-1 cells to suppress the expression of SR-A. We also analyzed the binding of nonlabeled CRP to immobilized recombinant LOX-1 and SR-A in vitro using anti-CRP antibody. COS-7 cells expressing LOX-1 and SR-A internalized fluorescently labeled CRP in a dose-dependent manner, but cells expressing CD36, SR-BI, or CD68 did not. The recombinant LOX-1 and SR-A proteins recognized nonlabeled purified CRP and native CRP in serum in vitro. THP-1 cells differentiated into macrophage-like cells by treatment with PMA-internalized fluorescently labeled CRP. siRNA against SR-A significantly and concomitantly inhibited the expression of SR-A (P < 0.01) and CRP uptake (P < 0.01), whereas control siRNA did not. CRP is recognized by SR-A as well as LOX-1 and taken up via SR-A in a macrophage-like cell line. This process might be of significance in the pathogenesis of atherosclerotic disease.