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Title: CAROTENOIDS NORMALLY PRESENT IN SERUM INHIBIT PROLIFERATION AND INDUCE DIFFERENTIATION OF A HUMAN MONOCYTE/MACROPHAGE CELL LINE (U937)

Author
item MCDEVITT, THERESA - UNIV SCIENCES,PHIL. PA
item TCHAO, RUY - UNIV SCIENCES,PHIL. PA
item Harrison, Earl
item MOREL, DIANE - UNIV SCIENCES,PHIL. PA

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/1/2004
Publication Date: 1/20/2005
Citation: Mcdevitt, T.M., Tchao, R., Harrison, E.H., Morel, D.W., 2005. Carotenoids normally present in serum inhibit proliferation and induce differentiation of a human monocyte/macrophage cell line (U937). Journal of Nutrition. 135:160-164.

Interpretive Summary: Carotenoids are plant pigments that give fruits and vegetables their yellow, orange, and red colors, and they are implicated in chronic disease protection. They are absorbed from the diet and transported in blood. Monocytes, as circulating blood cells, are exposed to carotenoids in blood. Such exposure may lead to enrichment with carotenoids and may affect the functions of these cells. This study explored the impact of cellular enrichment with beta-carotene, lycopene, or lutein on monocyte function, using a cell culture model. Beta-Carotene, lycopene and lutein markedly inhibited proliferation of cells. Since proliferation of these cells may be involved in several disease processes, including heart disease, these results suggest a way by which diet can affect disease risk. This work will be of use to nutritional scientists and health professionals in trying to understand the basis of the protective effects of fruit and vegetable intake on the risk of chronic diseases.

Technical Abstract: Carotenoids, plant pigments with potent antioxidant activity, are implicated in chronic disease protection. They are absorbed from the diet and transported by plasma lipoproteins. Monocytes, as circulating blood cells, are exposed to carotenoid-rich lipoproteins. Such exposure may lead to enrichment with carotenoids and may affect the functions of monocyte-derived macrophages. This study explored the impact of cellular enrichment in vitro with '-carotene, lycopene, or lutein on monocyte/macrophage function, using U937 cells as a model. Cell proliferation, production of reactive oxygen species, and cell-substrate adhesion were examined. Maximal carotenoid levels in medium supplemented with pre-enriched human serum were 2-8 x 10'6 mol/L; incubation for 1-6 days resulted in 0.2-1.1 nmol carotenoid/mg cell protein (0.25-1 nmol/ 106 cells), about 10-fold less than that reported in normal tissue in vivo but within the range that might be anticipated with dietary supplementation. Beta-carotene, lycopene and lutein markedly inhibited proliferation of U937 cells, to an extent similar to or greater than that observed with phorbol myristic acetate, a known differentiation/activation agent. Lycopene, but not beta-carotene or lutein, caused a significant increase in reactive oxygen species indicating the induction of cell differentiation. Adhesion and LDL oxidation were unaffected. Thus, cellular carotenoids inhibit proliferation, and for lycopene at least, this may involve cell differentiation. The effectiveness of lycopene, a non provitamin A carotenoid, is consistent with a retinoid-independent pathway modulating cell function.