Synergically Increased Expression of CD36, CLA-1 and CD68, but Not of SR-A and LOX-1, with the Progression to Foam Cells from Macrophages.

Abstract

Several species of scavenger receptors have so far been identified. However, it remains unclear which receptors are more crucial for the foam cell formation and progression. In the present study, we compared five major scavenger receptors (SR-A, CD36, CLA-1, CD68, and LOX-1) in their levels of expression at the different stages of foam cells derived from THP-1 cells. The expression of all scavenger receptors examined was up-regulated by the stimulation with TPA for 48 hours, despite the expressions of SR-A, CD36 and LOX-1 being very low before the treatment with TPA. Four to 7 days after the removal of TPA, the levels of CD36, CLA-1 and CD68 were increased significantly. In contrast, the expression of SR-A was suppressed significantly, and no change was observed in that of LOX-1. Furthermore, when the transformed macrophages were incubated with oxidized LDL, in which the uptake of [3H] cholesteryl oleoyl ether-labeled OxLDL was linear up to 7 days after the addition of OxLDL, the expression of CD36, CLA-1 and CD68 were greatly enhanced. This enhancement was more prominent than that without oxidized LDL, and the enhancement was sustained throughout the experimental period. On the other hand, SR-A was not up-regulated, and LOX-1 was down-regulated. We thus propose that CD36, CLA-1 and CD68, but not SR-A and LOX-1, may play crucial roles in the progression of macrophages to foam cells, which is a key step for the initiation of atherosclerosis.

GroEL1, a Heat Shock Protein 60 of Chlamydia pneumoniae, Induces Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Expression in Endothelial Cells and Enhances Atherogenesis in Hypercholesterolemic Rabbits

“…Specific oxLDL receptors including LOX-1 and scavenger receptors have been described in endothelial cells, macrophages, and smooth muscle cells. These receptors facilitate uptake of oxLDL and subsequent endothelial activation, transformation of macrophages to foam cells, and smooth muscle cell proliferation (38,39). In the current study, we demonstrated that GroEL1 upregulates LOX-1 expression in HCAECs.…”

CD68/macrosialin: not just a histochemical marker

“…58,59 In contrast to macrophages, 59 CD68 is not expressed by dendritic cells (DCs) 14,60 and this helps to immunohistochemically distinguish these two cell types, both of which have antigenpresenting capabilities. Several studies have shown significant upregulation of CD68 expression in macrophages in response to inflammatory stimuli such as exposure to oxLDL 12,49,50 and chronic stimulation with bacterial lipopolysaccharide (LPS) or inflammatory cytokine interferon-γ (IFN-γ). In microglial cells (brain tissue-resident macrophages), CD68 expression was stimulated by LPS and IFN-γ in a Toll-like receptor 4 (TLR4)-dependent manner.…”

“…49 THP-1 monocytic cells exposed to oxLDL had upregulated expression of scavenger receptors CD36, CLA-1, and CD68 (but not LOX-1 and SR-A1) and increased oxLDL uptake. 50 In vivo studies that assessed a role of CD68 in atherosclerosis were performed in APA hamsters that develop atheromatous plaques in streptozotocin-induced diabetes. In such a model of diabetic atherosclerosis, rabbits develop early lesions (fatty streaks) by 6 weeks after streptozotocin administration along with hyperlipidemia.…”

Proinflammatory Cytokines Regulate LOX-1 Expression in Vascular Smooth Muscle Cells

“…In vitro LOX-1 binds oxidized LDL, and this modified lipoprotein upregulates LOX-1 expression in EC 12,13 and SMC, 14 but downregulates this receptor in M⌽. 15 Atherosclerotic lesions containing lipid-laden foam cells are the hallmark of the inflammatory state, and recent investigations showed that inflammatory stimuli modulate LOX-1 expression in vitro. IL-4 induces LOX-1 expression in M⌽ 16 and tumor necrosis factor (TNF)-␣ and transforming growth factor (TGF)-␤ upregulate LOX-1 expression in EC, 17,18 M⌽, 18 -20 and SMC.…”