Feldman D L, Mogelesky T C, Liptak B F, Gerrity R G
Department of Pharmacology and Chemotherapy, Hoffmann-La Roche, Nutley, N.J.
Arterioscler Thromb. 1991 Jul-Aug;11(4):985-94. doi: 10.1161/01.atv.11.4.985.
In cholesterol-fed rabbits the extent of monocyte involvement in atherogenesis may be influenced by the level of circulating leukocytes during hypercholesterolemia. We characterized the leukocytosis in rabbits fed either a 0.25% or a 0.1% cholesterol-enriched diet (0.25% or 0.1% rabbits, respectively). Circulating leukocytes were elevated by 1 week of feeding, and the elevation was sustained for at least 30 weeks. Differential counts were unchanged. Immature leukocytes were not seen, indicating that the leukocytosis was not due to premature release of bone marrow cells. Animals were free of bacterial or parasitic disease; selected rabbits with leukocytosis had normal body temperatures. Spleen weights averaged at least 100% higher in 0.25% rabbits but did not show histological evidence for hematopoiesis that could account for the leukocytosis. At approximately 22 weeks there was a second rise in leukocytosis in bilirubinemic 0.25% rabbits, suggesting that in the late stages of hypercholesterolemia, leukocytosis is related to liver failure. Cholesterol-fed rabbits also showed thrombocytosis. Existing leukocytosis and hypercholesterolemia were reversed to pretreatment levels by switching the rabbits to chow diets. In bone marrow from 0.25% rabbits, the mean number of cells per gram was greater (p less than 0.05) than that from normocholesterolemic rabbits. In 0.25% rabbits, the fraction of blood mononuclear cells showing phagocytosis of immunoglobulin G-coated red blood cells did not differ from that of controls, suggesting an unchanged population of these cells with regard to Fc and phagocytic function during hypercholesterolemia. These data suggest an effect (direct or indirect) of hypercholesterolemia on the production of leukocytes in the bone marrow and/or on the circulation kinetics of leukocytes in the blood.
在喂食胆固醇的兔子中，单核细胞参与动脉粥样硬化形成的程度可能受高胆固醇血症期间循环白细胞水平的影响。我们对分别喂食0.25%或0.1%富含胆固醇饮食的兔子（分别称为0.25%兔子和0.1%兔子）的白细胞增多症进行了表征。喂食1周后循环白细胞升高，并持续至少30周。分类计数没有变化。未见到未成熟白细胞，这表明白细胞增多症不是由于骨髓细胞过早释放所致。动物没有细菌或寄生虫疾病；选定的白细胞增多症兔子体温正常。0.25%兔子的脾脏重量平均至少高出100%，但未显示出可解释白细胞增多症的造血组织学证据。在大约22周时，患黄疸的0.25%兔子的白细胞增多症出现第二次升高，这表明在高胆固醇血症后期，白细胞增多症与肝功能衰竭有关。喂食胆固醇的兔子还出现血小板增多症。将兔子改喂普通饮食后，现有的白细胞增多症和高胆固醇血症恢复到预处理水平。在0.25%兔子的骨髓中，每克细胞的平均数量比正常胆固醇水平兔子的多（p小于0.05）。在0.25%兔子中，显示吞噬免疫球蛋白G包被红细胞的血液单核细胞比例与对照组没有差异，这表明在高胆固醇血症期间，这些细胞在Fc和吞噬功能方面的群体没有变化。这些数据表明高胆固醇血症对骨髓中白细胞的产生和/或血液中白细胞的循环动力学有（直接或间接）影响。
