Expression of the novel scavenger receptor SR-PSOX in cultured aortic smooth muscle cells and umbilical endothelial cells.

SR-PSOX in Cultured Aortic Smooth Muscle Cells and Umbilical Endothelial Cells To the Editor: In the November issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Minami et al1 demonstrated expression of the novel scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) in lipid-laden macrophages accumulated in the intima of human atherosclerotic lesions. Because SR-PSOX seems to be identical to the membrane-anchored chemokine CXCL16,2,3 which may play a dual role in inflammation and homeostasis, Minami et al1 discussed the potential regulation of SR-PSOX by pro-inflammatory cytokines. Although the authors did not detect SR-PSOX in smooth muscle cells (SMCs) and endothelial cells (ECs), they did discuss the possible expression of SR-PSOX in these cell types. Until now, only the expression of the scavenger receptors SR-AI/II,4 CD36,5 and LOX-16 in SMCs has been described. In our studies on the formation of SMC-derived foam cells during atherogenesis, we have focused on the expression of scavenger receptors,7 including SR-PSOX, in SMCs and ECs. We have also investigated the influence of cytokines on the expression of SR-PSOX in SMCs. Reverse transcriptase–polymerase chain reaction (PCR; primers for human SRPSOX: 5 -TACACGAGGTTCCAGCTCCT-3 and 5 -GGGGGCTGGTAGGAAGTAAA-3 , porcine SR-PSOX: 5 -TATGTGGAGGCAGCAGTGAC-3 and 5 -CTGCAGGGTAGATGGCAGAT-3 ) was performed on total RNA from cultured human and porcine aortic SMCs and human umbilical vein endothelial cells (HUVECs). PCR was performed at 94°C (45 seconds), 58°C (60 seconds), and 72°C (60 seconds) for 20 to 40 cycles in the linear area of amplification. The sequences of SR-PSOX products were confirmed by sequence analysis. -Actin served as the internal standard. Thus, reverse transcriptase–PCR demonstrated the expression of SR-PSOX mRNA in porcine and human aortic SMCs and HUVECs as well as in human monocyte-derived macrophages, which were used as a positive control.8 In human SMCs, SR-PSOX was more strongly expressed than LOX-1 and SR-AI/II (29 to 31 versus 38 to 40 cycles). The SR-PSOX–mediated uptake of oxidized LDL in synthetic SMCs is possibly as strong as or even stronger than that mediated by LOX-1 or SR-AI/II. Because SR-PSOX/CXCL16 possibly plays a role in inflammation2,3 and because several scavenger receptors are regulated by pro-inflammatory cytokines,9 we investigated the influence of tumor necrosis factor(TNF), interleukin-1 (IL-1 ), and interferon(IFN) on the expression of SR-PSOX in SMCs. However, in contrast to the scavenger receptor SR-AI/II, which is stimulated by TNF, IL-1 , and IFN,10,11 and to LOX-1, which is stimulated by TNF,12 SR-PSOX mRNA expression was not influenced by these cytokines (Figure, IFNnot shown). The reported induction of LOX-1 expression by TNF12 was confirmed (data not shown) and served as a positive control. SR-PSOX does not share any homology with other scavenger receptors, except a mucin-like domain also found in SR-CI13 and CD68/macrosialin,14 and obviously SR-PSOX is regulated via different mechanism than those described for SR-AI/II and LOX-1. In summary, we demonstrate that the scavenger receptor SR-PSOX, which is expressed in human atherosclerotic lesions and may be involved in foam cell formation, is not only expressed in macrophages, but also in cultured SMCs and HUVECs. Moreover, our data indicate that SR-PSOX is governed by pathways other than those reported for SR-AI/II and LOX-1. Further studies will elucidate the functional role of SR-PSOX and its regulation in SMCs and ECs.