CELL BIOLOGY. For the article “Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARγ agonist,” by Thomas M. McIntyre, Aaron V. Pontsler, Adriana R. Silva, Andy St. Hilaire, Yong Xu, Jerald C. Hinshaw, Guy A. Zimmerman, Kotaro Hama, Junken Aoki, Hiroyuki Arai, and Glenn D. Prestwich, which appeared in number 1, January 7, 2003, of Proc. Natl. Acad. Sci. USA (100, 131–136; First Published December 26, 2002; 10.1073/pnas.0135855100), Fig. 4 should have appeared in color. The correct figure and its legend appear below.
Figure 4.
LPA stimulates lipid accumulation, CD36 expression, and oxidized LDL uptake through a PPAR-responsive element. (a) LPA stimulates monocyte uptake of oxidized LDL. Freshly elutriated human monocytes were allowed to interact with an anti-ICAM3-coated well, which leads to rapid PPARγ expression (13), and then stimulated, or not (negative, oxLDL), with oleoyl LPA. Some cells were then briefly exposed to oxidized LDL before intracellular lipid stores were visualized with oil red O stain. (b) LPA increases the expression of CD36 on the surface of primary human monocytes. Monocytes engaging anti-ICAM3 were treated or not with LPA, and then recovered by gentle scraping and washing by centrifugation before their surface CD36 was assessed by flow cytometry. (c) LPA and the LPA analogs XY4 and XY8 stimulate CD36 promoter function only when the PPRE is present. RAW264.7 cells were transfected with the human CD36 promoter containing the PPRE (CD36−273) or a reporter that lacks only this element (CD36−261) and then stimulated with oleoyl LPA, azPC, XY4, or XY8. Expression of luciferase normalized to β-galactosidase was determined as above. (d) Anti-CD36 blocks LPA-stimulated accumulation of cholesterol from oxidized LDL. Freshly isolated human monocytes were treated as in a, but after being preincubated with a blocking anti-CD36 antibody before exposure to oxidized LDL.