Suppressive Effect of β-Carotene on the Development of Pulmonary Foam Cells in Rats with Hyper β-Lipoproteinemia

Abstract

The effect of β-carotene (BC) on the development of pulmonary foam cells (PFCs) was studied in rats with diet-induced hyper β-lipoproteinemia. Rats were fed a standard diet; a hyper-β-lipoproteinemic diet (HB) consisting of the standard diet, 4% cholesterol, and 1% cholic acid; or the standard diet plus 0.1% BC; or the HB diet plus 0.1% BC diet (HBC). Rats in the HB and HBC groups developed hyper-β-lipoproteinemia, but no significant differences were observed in serum levels of total cholesterol, phospholipid, and β- lipoprotein (B-LP) between both groups. The percentages of foamy, lipid-ingested monocytes (FMs) to the number of blood monocytes (BMs), the number and size of lipid droplets in FMs, the percentages of PFCs to the number of alveolar macrophages from bronchopulmonary lavage fluid, and the score of PFC development in the lungs of rats in the HBC group were reduced compared to those of rats in the HB group. There were no differences in latex-phagocytotic activity of BMs among rats in the control, HB, BC, and HBC groups. BC suppressed the foamy transformation of BMs and development of PFCs deriving from the influx of FMs into the alveoli of hyper-β-lipoproteinemic rats. Based on the present results, it is presumed that the antioxidative property of BC may prevent an oxidative modification of B-LP under the hyper-β-lipoproteinemic condition, leading to a decrease in the uptake of oxidatively modified B-LP by BMs.

Keywords

Alveolar macrophage antioxidant cytology foamy transformation histopathology monocyte lipoprotein oxidation phagocytosis

References

Bálint A. , Veress B. , Nagy Z. , and Jellinek H. (1972). Role of lipophages in the development of rat atheroma . Atherosclerosis 15: 7-15.

Blussé Van Oud Alblas A and Van Furth R. (1979). Origin, kinetics, and characteristics of pulmonary macrophages in the normal steady state. J. Exp. Med. 149:1504-1518.

Bowden DH and Adamson IYR (1980). Role of monocytes and interstitial cells in the generation of alveolar macrophages: I. Kinetic studies of normal mice. Lab. Invest. 42: 511-517.

Boyd HC , Gown AM , Wolfbauer G. , and Chait A. (1989). Direct evidence for a protein recognized by a monoclonal antibody against oxidatively modified LDL in atherosclerotic lesions from a Watanabe heritable hyperlipidemic rabbit. Am. J. Pathol . 135:815-825.

Brown MS and Goldstein JL (1983). Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Annu. Rev. Biochem. 52: 223-261.

Burton GW and Ingold KU (1984). β-carotene: An unusual type of lipid antioxidant . Science 224: 569-573.

Carew TE , Schwenke DC , and Steinberg D. (1987). Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: Evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc. Natl. Acad. Sci. USA 84: 7725-7729.

Goldstein JL , Ho YK , Basu SK , and Brown MS (1979). Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc. Natl. Acad. Sci. USA 76: 333-337.

Henriksen T. , Mahoney EM , and Steinberg D. (1983). Enhanced macrophage degradation of biologically modified low density lipoprotein . Arteriosclerosis 3: 149-159.

10.

Heywood R. , Palmer AK , Gregson RL , and Hummler H. (1985). The toxicity of beta-carotene. Toxicology 36:91-100.

11.

Hoff HF and Cole TB (1991). Macrophage uptake of low-density lipoprotein modified by 4-hydroxynonenal: An ultrastructural study. Lab. Invest . 64: 254-264.

12.

Krinsky NI and Deneke SM (1982). Interaction of oxygen and oxy-radicals with carotinoids . J. Natl. Cancer Inst. 69: 205-210.

13.

Kunert K-J. and Tappel AL (1983). The effect of vitamin C on in vivo lipid peroxidation in guinea pigs as measured by pentane and ethane production. Lipids 18: 271-274.

14.

Marshall JR and O'Neal RM (1966). The lipophage in hyperlipemic rats: An electron microscopic study. Exp. Mol. Pathol. 5: 1-11.

15.

Mathews-Roth MM (1988). Lack of genotoxicity with beta-carotene. Toxicol. Lett. 41: 185-191.

16.

Mitchinson MJ and Ball RY (1987). Macrophages and atherosclerosis . Lancet 2: 146-149.

17.

Palinski W. , Rosenfeld ME , Ylä-Herttuala S. , Gurtner GC , Socher SS , Butler SW , Parthasarathy S. , Carew TE , Steinberg D. , and Witztum JL (1989). Low density lipoprotein undergoes oxidative modification in vivo. Proc. Natl. Acad. Sci. USA 86: 1372-1376.

18.

Parthasarathy S. , Young SG , Witztum JL , Pittman RC , and Steinberg D. (1986). Probucol inhibits oxidative modification of low density lipoprotein. J. Clin. Invest. 77: 641-644.

19.

Phizackerley PJR , Newman GE , Smith H. , and Cooper JR (1983). The reversible detachment and deposition of surfactant and of pulmonary macrophages during bronchopulmonary lavage in the rat. J. Pathol. 140: 1-7.

20.

Salisbury BGJ , Falcone DJ , and Minick CR (1985). Insoluble low-density lipoprotein-proteoglycan complexes enhance cholesteryl ester accumulation in macrophages. Am. J. Pathol. 120: 6-11.

21.

Shibuya K. , Tajima M. , Yamate J. , Ihara M. , and Kudow S. (1989). Influence of cholesterol administration and aging on the development of pulmonary foam cells in F344 rats. Jpn. J. Vet. Sci. 51: 1017-1024.

22.

Shibuya K. Tajima M. Yamate J. Saitoh T. and Sannai S. (1991). Genesis of pulmonary foam cells in rats with diet-induced hyper beta-lipoproteinemia. Int. J. Exp. Pathol. 72: 423-435.

23.

Simon RC , Still WJS , and O'Neal RM (1961). The circulating lipophage and experimental atherosclerosis . J. Atheroscler. Res. 1: 395-400.

24.

Steinbrecher UP , Parthasarathy S. , Leake DS , Witztum JL , and Steinberg D. (1984). Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc. Natl. Acad. Sci. USA 81: 3883-3887.

25.

Stocker R. , Bowry VW , and Frei B. (199 1). Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol. Proc. Natl. Acad. Sci. USA 88: 1646-1650.

26.

Suits AG , Chait A. , Aviram M. , and Heinecke JW (1989). Phagocytosis of aggregated lipoprotein by macrophages: Low density lipoprotein receptor-dependent foam-cell formation. Proc. Natl. Acad. Sci. USA 86: 2713-2717.

27.

Ylä-Herttuala S. , Palinski W. , Rosenfeld ME , Parthasarathy S. , Carew TE , Butler S. , Witztum JL , and Steinberg D. (1989). Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J. Clin. Invest . 84: 1086-1095.

28.

Yokode M. , Kita T. , Kikawa Y. , Ogorochi T. , Narumiya S. , and Kawai C. (1988). Stimulated arachidonate metabolism during foam cell transformation of mouse peritoneal macrophages with oxidized low density lipoprotein. J. Clin. Invest. 81: 720-729.