Bermudez L E, Young L S, Gupta S
Kuzell Institute for Arthritis & Infectious Diseases, San Francisco, California.
Cell Immunol. 1990 May;127(2):432-41. doi: 10.1016/0008-8749(90)90144-g.
Vitamin D3 (D3) has been shown to activate several macrophage functions. To determine whether D3 could activate macrophages to kill or inhibit intracellular growth of Mycobacterium avium complex (MAC), human monocyte-derived macrophages were treated with D3 (10(-7), 10(-8), and 10(-9) M) 24 hr before or for 48 hr after MAC infection. All three concentrations were associated with inhibition of growth or killing of MAC in a dose-dependent fashion (28 +/- 4% and 22 +/- 3% of killing and inhibition of growth, respectively, at pharmacological concentrations) when added to the monolayer before injection or 60.4 +/- 6%, 50.4 +/- 3%, and 41.4 +/- 6%, respectively, when added to the monolayers after infection. We found that D3-treated macrophages produced increased concentrations of tumor necrosis factor (TNF) and granulocyte-monocyte colony stimulating factor (GM-CSF). Subsequently, macrophages were activated by D3 in the presence of anti-TNF or anti-GM-CSF antibody: At 10(-9) M of D3 there was no inhibition of D3-dependent macrophage activation by anti-TNF antibody, whereas anti-GM-CSF antibody was associated with 100% inhibition. At 10(-8) M of D3, anti-TNF antibody inhibited 35 +/- 6% of killing, and anti-GM-CSF antibody was associated with 100% inhibition. At 10(-7) M of D3, anti-TNF antibody inhibited 58 +/- 4% and anti-GM-CSF antibody 89 +/- 3% of killing. D3 treatment is associated with anti-MAC activity in human macrophages, and this activity appears to be mediated by both TNF and GM-CSF.
维生素D3（D3）已被证明可激活多种巨噬细胞功能。为了确定D3是否能激活巨噬细胞以杀死或抑制鸟分枝杆菌复合群（MAC）的细胞内生长，在MAC感染前24小时或感染后48小时，用D3（10^(-7)、10^(-8)和10^(-9) M）处理人单核细胞衍生的巨噬细胞。当在注射前添加到单层细胞中时，所有三种浓度均以剂量依赖方式抑制MAC的生长或杀伤（在药理浓度下，杀伤和生长抑制分别为28±4%和22±3%）；当在感染后添加到单层细胞中时，分别为60.4±6%、50.4±3%和41.4±6%。我们发现，经D3处理的巨噬细胞产生的肿瘤坏死因子（TNF）和粒细胞-单核细胞集落刺激因子（GM-CSF）浓度增加。随后，在存在抗TNF或抗GM-CSF抗体的情况下，巨噬细胞被D3激活：在10^(-9) M的D3浓度下，抗TNF抗体未抑制D3依赖性巨噬细胞激活，而抗GM-CSF抗体导致100%的抑制。在10^(-8) M的D3浓度下，抗TNF抗体抑制35±6%的杀伤，抗GM-CSF抗体导致100%的抑制。在10^(-7) M的D3浓度下，抗TNF抗体抑制58±4%的杀伤，抗GM-CSF抗体抑制89±3%的杀伤。D3处理与人巨噬细胞中的抗MAC活性相关，并且这种活性似乎由TNF和GM-CSF共同介导。
