Badger A M, Hutchman J S, Sung C P, Bugelski P J
Department of Immunology and Anti-infectives Therapy, Smith Kline and French Laboratories, Swedeland, Pennsylvania 19479.
J Leukoc Biol. 1987 Nov;42(5):447-54. doi: 10.1002/jlb.42.5.447.
We have investigated the effects of murine interferons on the ability of rat alveolar macrophages (AM) to inhibit the proliferation of the intracellular protozoan Toxoplasma gondii. This activity was determined by measuring suppression of 3H-uracil uptake into the Toxoplasma and by microscopic enumeration of the intracellular organisms. Recombinant gamma interferon (rMulFN-gamma), but not alpha/beta interferon (IFN-alpha/beta) was able to activate AM for antimicrobial activity in vitro. Maximum activation was achieved by incubation with 50-200 units/ml rMulFN-gamma and the activity was lost at one unit/ml. The highest levels of activation were obtained when macrophages were incubated with interferon for 48-72 h prior to the challenge with Toxoplasma organisms. Activation could still be obtained, however, when the interferon was added to the cultures as late as 2 h after the phagocytosis of Toxoplasma. Neither MDP nor low concentrations (1-1-ng/ml) of S. typhosa lipopolysaccharide (LPS) were able to activate these cells to inhibit the growth of Toxoplasma. Phagocytosis of Toxoplasma by AM did not result in the release of O2-, in fact the spontaneous release of O2- by these cells was inhibited by Toxoplasma. This inhibition was reversed by preincubation of the cells with rMulFN-gamma.
我们研究了鼠干扰素对大鼠肺泡巨噬细胞（AM）抑制细胞内原生动物刚地弓形虫增殖能力的影响。通过测量3H-尿嘧啶掺入弓形虫的抑制情况以及通过显微镜计数细胞内生物体来确定这种活性。重组γ干扰素（rMulFN-γ），而非α/β干扰素（IFN-α/β），能够在体外激活AM的抗菌活性。通过与50 - 200单位/毫升的rMulFN-γ孵育可实现最大激活，且在1单位/毫升时活性丧失。当巨噬细胞在用弓形虫生物体攻击前与干扰素孵育48 - 72小时时，可获得最高水平的激活。然而，即使在吞噬弓形虫后2小时才将干扰素添加到培养物中，仍可获得激活。MDP和低浓度（1 - 1纳克/毫升）的伤寒沙门氏菌脂多糖（LPS）均不能激活这些细胞来抑制弓形虫的生长。AM对弓形虫的吞噬并未导致O2-的释放，事实上这些细胞O2-的自发释放受到弓形虫的抑制。用rMulFN-γ对细胞进行预孵育可逆转这种抑制。
