Newman G W, Gan H X, McCarthy P L, Remold H G
Department of Rheumatology/Immunology, Brigham and Womens Hospital, Harvard Medical School, Boston, MA 02115.
J Immunol. 1991 Dec 1;147(11):3942-8.
The long term survival of peripheral blood derived human macrophages (M phi) from normal, healthy donors after infection with Mycobacterium avium intracellulare (MAI) correlates with the increased induction of TNF-alpha and IL-6 mRNA and protein by the infected M phi. This conclusion is based on the following observations: M phi from approximately 30% of the blood donors in our study die 3 to 4 days after inoculation (MAI-growth nonsupportive (NS], whereas M phi from the other donors survive inoculation with MAI for 7-10 days (MAI-growth supportive (S)). S-type M phi when infected with MAI had markedly increased amounts of TNF-alpha and IL-6 mRNA and protein when compared to NS-type M phi. The effect of LPS on the induction of TNF-alpha mRNA and protein was also significantly enhanced in S-type M phi in comparison to NS cells. In contrast, IL-1 beta mRNA and protein production had similar increases in both donor types when infected with MAI or stimulated with LPS. The phenotype of the donors in the amount of TNF-alpha and IL-6 produced in response to MAI infection remained stable for a period of more than 1 yr. Pretreatment of NS M phi with recombinant human granulocyte-macrophage-CSF, but not IFN-gamma, however, converted NS M phi into a S-type cell phenotype. These granulocyte-macrophage-CSF pretreated NS M phi survived infection with MAI for a longer period of time and also had increased production of both TNF-alpha and IL-6 mRNA and protein. Cultures of S-type M phi infected with MAI had higher numbers of intracellular bacteria when compared to cultures of NS-infected M phi. Thus, increased survival of MAI-infected human M phi in vitro is correlated to increased production of TNF-alpha and IL-6 in response to infection with MAI.
来自正常健康供体的外周血源性人类巨噬细胞（M phi）在感染鸟分枝杆菌胞内菌（MAI）后的长期存活与被感染的M phi中TNF-α和IL-6 mRNA及蛋白诱导增加相关。这一结论基于以下观察结果：在我们的研究中，约30%的献血者的M phi在接种后3至4天死亡（MAI生长非支持性（NS）），而其他供体的M phi在接种MAI后存活7至10天（MAI生长支持性（S））。与NS型M phi相比，S型M phi感染MAI后TNF-α和IL-6 mRNA及蛋白的量显著增加。与NS细胞相比，LPS对S型M phi中TNF-α mRNA和蛋白诱导的作用也显著增强。相反，当感染MAI或用LPS刺激时，两种供体类型中IL-1β mRNA和蛋白的产生均有类似增加。供体对MAI感染产生的TNF-α和IL-6量的表型在超过1年的时间内保持稳定。然而，用重组人粒细胞-巨噬细胞集落刺激因子（而非IFN-γ）预处理NS M phi可将其转化为S型细胞表型。这些经粒细胞-巨噬细胞集落刺激因子预处理的NS M phi在感染MAI后存活更长时间，并且TNF-α和IL-6 mRNA及蛋白的产生也增加。与NS感染的M phi培养物相比，感染MAI的S型M phi培养物中的细胞内细菌数量更多。因此，体外MAI感染的人类M phi存活增加与感染MAI后TNF-α和IL-6产生增加相关。
