Yoshida N, Yoshikawa T, Manabe H, Terasawa Y, Kondo M, Noguchi N, Niki E
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
J Leukoc Biol. 1999 Jun;65(6):757-63. doi: 10.1002/jlb.65.6.757.
We evaluated the effects of alpha-Toc on surface expression of CD11b/CD18 on polymorphonuclear leukocytes (PMN) stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and oxidized low-density lipoprotein (oxLDL). Incubation of PMN with fMLP (1 microM) or oxLDL (100 microg/mL) increased CD11b/CD18 expression; pretreatment with alpha-Toc reduced in a dose-dependent manner. PMN obtained from healthy adults ingesting 600 mg alpha-Toc per day for 10 days were similarly incubated with fMLP or oxLDL; the surface level of CD11b/CD18 was inversely correlated with serum alpha-Toc concentrations. Adherence of PMN to human umbilical vein endothelial cells was increased by fMLP or oxLDL stimulation but reduced by alpha-Toc pretreatment or anti-CD18 monoclonal antibodies. cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) activity in PMN was also assayed. A PKC inhibitor, but not a PKA inhibitor, suppressed CD11b/CD18 up-regulation, and alpha-Toc slightly decreased fMLP- and oxLDL-induced activation of PKC. These results suggest that alpha-Toc may prevent inflammation by both reducing CD11b/ CD18 up-regulation and decreasing PMN-dependent adherence to EC.
我们评估了α-生育酚对用N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）和氧化低密度脂蛋白（oxLDL）刺激的多形核白细胞（PMN）上CD11b/CD18表面表达的影响。用fMLP（1μM）或oxLDL（100μg/mL）孵育PMN会增加CD11b/CD18的表达；用α-生育酚预处理会以剂量依赖的方式降低其表达。从每天摄入600mgα-生育酚，持续10天的健康成年人中获取的PMN，同样用fMLP或oxLDL进行孵育；CD11b/CD18的表面水平与血清α-生育酚浓度呈负相关。fMLP或oxLDL刺激会增加PMN对人脐静脉内皮细胞的黏附，但α-生育酚预处理或抗CD18单克隆抗体可降低这种黏附。我们还检测了PMN中cAMP依赖性蛋白激酶（PKA）和蛋白激酶C（PKC）的活性。一种PKC抑制剂而非PKA抑制剂可抑制CD11b/CD18的上调，并且α-生育酚可轻微降低fMLP和oxLDL诱导的PKC活化。这些结果表明，α-生育酚可能通过减少CD11b/CD18的上调以及降低PMN依赖性的对内皮细胞的黏附来预防炎症。
