Wu-Hsieh B A, Chen W, Lee H J
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Infect Immun. 1998 Nov;66(11):5520-6. doi: 10.1128/IAI.66.11.5520-5526.1998.
Splenic macrophages from Histoplasma capsulatum-infected mice express inducible nitric oxide synthase (iNOS), and the iNOS expression correlates with severity of the infection. We examined whether production of NO is responsible for apoptosis and the anti-lymphoproliferative response of splenocytes from mice infected with H. capsulatum. In situ terminal deoxynucleotidyl transferase nick end labeling revealed apoptotic nuclei in cryosections of spleen from infected but not normal mice. Splenocytes of infected mice were unresponsive to stimulation by either concanavalin A or heat-killed H. capsulatum yeast cells. Splenocyte responsiveness was restored by addition to the medium of NG-monomethyl-L-arginine, a known inhibitor of NO production. The proliferative response of splenocytes from infected mice was also restored by depletion of macrophages or by replacement with macrophages from normal mice. In addition, expression of iNOS returned to its basal level when the animals had recovered from infection. These results suggest that suppressor cell activity of macrophages is associated with production of NO, which also appears to be an effector molecule for apoptosis of cultured splenocytes from infected mice.
来自荚膜组织胞浆菌感染小鼠的脾巨噬细胞表达诱导型一氧化氮合酶（iNOS），且iNOS表达与感染的严重程度相关。我们研究了一氧化氮（NO）的产生是否与荚膜组织胞浆菌感染小鼠脾细胞的凋亡及抗淋巴细胞增殖反应有关。原位末端脱氧核苷酸转移酶缺口末端标记显示，在感染小鼠而非正常小鼠的脾脏冰冻切片中有凋亡细胞核。感染小鼠的脾细胞对刀豆球蛋白A或热灭活的荚膜组织胞浆菌酵母细胞的刺激无反应。通过向培养基中添加NG-单甲基-L-精氨酸（一种已知的NO产生抑制剂），脾细胞反应性得以恢复。通过去除巨噬细胞或用正常小鼠的巨噬细胞替代，感染小鼠脾细胞的增殖反应也得以恢复。此外，当动物从感染中恢复时，iNOS的表达恢复到基础水平。这些结果表明，巨噬细胞的抑制细胞活性与NO的产生有关，NO似乎也是感染小鼠培养脾细胞凋亡的效应分子。
