Enhancement of the Expression of Activation Markers on Human Peripheral Blood Mononuclear Cells by In Vitro Culture With Retinoids and Carotenoids

Abstract

Retinoids (retinol, retinal, retinoic acid, retinyl beta-glucuronide, and 13-cis retinoic acid) and carotenoids (beta-carotene and canthaxanthin) were evaluated for their immunomodulatory effects on human peripheral blood T-lymphocyte subpopulations and natural killer (NK) cells. Peripheral blood mononuclear cells (PBMC) from healthy young volunteers were isolated and incubated for 72 hours at various levels of retinoids and carotenoids including a physiological concentration (10(-8) M). Expression of surface antigens for total T cells, T-helper and T-suppressor cells, and activation markers (transferrin receptor, HLA-Dr antigen, and interleukin 2 receptor) were analyzed with an EPICS V flow cytometer. Retinoic acid and 13-cis retinoic acid (13-cRA) produced significant increases in the percentage of cells with markers for total T-helper cells, with a minimal effect on percentage of lymphocytes with markers for NK cells. However, beta-carotene (BC), canthaxanthin (CTX), and retinyl beta-glucuronide (RBG) dramatically increased the percentage of PBMC with markers for NK cells and produced a smaller increase in lymphocytes with surface antigens identifying them as T-helper cells. Furthermore, retinol and retinal did not show significant change either in the percentage of lymphocytes with markers for T-helper cells or in the helper/suppressor ratio. An increase in the expression of HLA-Dr antigen and transferrin receptors was greater when cells were incubated with 13-cRA than with either BC, CTX, or RBG, while carotenoids produced a greater increase in the expression of IL-2 receptors than 13-cRA. Our study indicates that both retinoids and carotenoids might be activating different subpopulations of immune cells.

β-Carotene and the immune response

“…Vegetarians, whose vitamin A, vitamin E and vitamin C serum levels were equivalent to non-vegetarians, but whose @-carotene serum levels were twice as high as non-vegetarians, had twice the natural killer cell activity as the non-vegetarians (Malter et al 1989). Peripheral leucocyte cells from eleven adults, when cultured with 1 nM-@-carotene or 1nM-canthaxanthin for 72 h showed enhanced levels of cell surface markers indicative of natural killer cells, such as increases in surface markers for human leukocyte antigen-Dr, transferrin and interleukin 2 receptor (Prabhala et al 1989). Similar enhancement in these markers was also seen when elderly individuals were given @-carotene (30 mg/d for 2 months) (Watson et al 1991).…”

Tumouricidal activity of gilthead seabream (Sparus aurata L.) natural cytotoxic cells: the role played in vitro and in vivo by retinol acetate

“…On the other hand, incubation with 10 5 -10 7 M retinoic acid increased two-fold human natural killer (NK) cell activity [29] while it stimulated 20-fold the mouse cytotoxic T-cells activity [12]. A possible explanation for these results could be the finding that plasma membrane alterations and high surface receptor expression can be induced in human cytotoxic cells in vitro by retinoic acid [30,32].…”

Effects of Injectable β-Carotene and Vitamin A on Lymphocyte Proliferation and Polymorphonuclear Neutrophil Function in Piglets

“…They attributed this stimulatory effect to a direct carotenoid effect of p-carotene since canthaxanthin cannot be converted to vita min A. Other evidence for a specific role played by P-carotene have been provided by Prabhala et al [32] who showed that P-caro tene and canthaxanthin dramatically in creased natural killer cell population of hu man peripheral blood mononuclear cells and also produced a small increase in T-helper cells. In an earlier study, Alexander et al [ 14] similarly reported increased OKT4+ helper cells in human orally supplemented with Pcarotene.…”