T lymphocytes increase the synthesis of esterified cholesterol in human monocyte-derived macrophages by activation of the scavenger pathway.
Immunohistochemical analyses have shown the presence of T lymphocytes (T-cells) in atherosclerotic places in addition to macrophages and smooth muscle cells. To elucidate the role of T-cells in the formation of atherosclerotic lesions, we studied whether T-cells can stimulate the scavenger pathway and promote esterified cholesterol (EC) synthesis by [14C]oleate incorporation in macrophages. Macrophages and T-cells were co-cultured in two ways. In one culture, macrophages were in direct contact with T-cells (direct contact form). In the other, macrophages and T-cells were separated by Transwell membrane, but shared the same culture medium via the membrane (indirect contact form). Based on the incorporation of [14C]oleate into EC, macrophages strikingly increased EC synthesis in both forms of co-culture. This increase was proportional to the number of T-cells present and was inhibited by cyclosporin A. When macrophages were co-cultured indirectly in contact with T-cells in the presence of AcLDL for 24 h, and the T-cells were subsequently removed, EC synthesis in macrophages increased. However, this increase was not observed in macrophages that were rinsed twice with PBS. When macrophages, previously incubated with AcLDL for 24 h, were co-cultured indirectly in contact with T-cells for 24 h, the medium were prepared as activated T-cell-conditioned medium (aTCM). EC synthesis in macrophages cultured with aTCM increased. The ability of aTCM to increase EC synthesis disappeared upon repeated freezing/thawing, boiling and trypsin treatment. T-cells (indirect contact form) and aTCM similarly increased AcLDL-binding and -degradation in macrophages. These results indicated that T-cells secreted an active substance(s), protein in nature, which could activate the scavenger pathway and increase EC synthesis in macrophages. These observations suggest that T-cells can promote the uptake of modified lipoproteins by macrophages to induce foam cell-formation.
Kotake
H
H
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Oikawa
S
S
Naito
T
T
Hayasaka
K
K
Toyota
T
T
D001161:Arteriosclerosis / Q000276:immunology*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000096:biosynthesis*; D016572:Cyclosporine / Q000494:pharmacology; D005487:Foam Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008222:Lymphokines / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008222:Lymphokines; C032629:acetyl-LDL; D016572:Cyclosporine