Morahan P S, Dempsey W L, Volkman A, Connor J
Infect Immun. 1986 Jan;51(1):87-93. doi: 10.1128/iai.51.1.87-93.1986.
The effects of 89Sr treatment on the natural host resistance of CD-1 mice and the enhancement of resistance by immunomodulators to infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) were determined. In the CD-1 mouse, single-dose treatment with 89Sr caused a profound decrease in the number of circulating monocytes (Mo), lymphocytes, and polymorphonuclear leukocytes (PMN) within 1 week. There was also marked functional impairment of the Mo inflammatory response, as well as markedly decreased spontaneous and activatable cytotoxicity by splenic natural killer (NK) cells. Despite this profound cellular suppression, there was no significant change in natural resistance of CD-1 mice to L. monocytogenes or HSV-2 infection. Furthermore, prophylactic treatment of mice with the biologic immunomodulator Corynebacterium parvum or the synthetic immunomodulators maleic anhydride-divinyl ether or avridine in liposomes resulted in comparable enhancement of resistance in 89Sr-treated and normal mice. These data indicate that natural and immunomodulator-enhanced resistance of CD-1 mice to microbial infections do not depend on normal levels of Mo, PMN, or NK cells. The resistance enhancement may rely on activated tissue macrophages (M phi). In contrast to the early changes in circulating leukocytes, the resident peritoneal cell populations were not markedly altered until after day 30. There then was a distinct decline in lymphocytes and a gradual decline in M phi; the change in M phi was apparently due to the lack of an age-related increase in the peritoneal M phi population in 89Sr-treated mice in comparison with a slight increase in resident M phi in normal mice. After CD-1 mice were treated with 89Sr, the number of PMN and the function of NK cells generally recovered by about day 50 and was followed by partial recovery of circulating Mo, unless a second dose of 89Sr was administered.
研究了89Sr治疗对CD-1小鼠自然宿主抵抗力的影响，以及免疫调节剂对单核细胞增生李斯特菌或2型单纯疱疹病毒（HSV-2）感染抵抗力的增强作用。在CD-1小鼠中，单剂量89Sr治疗在1周内导致循环单核细胞（Mo）、淋巴细胞和多形核白细胞（PMN）数量显著减少。Mo炎症反应也有明显的功能损害，脾脏自然杀伤（NK）细胞的自发和可激活细胞毒性也显著降低。尽管有这种严重的细胞抑制，但CD-1小鼠对单核细胞增生李斯特菌或HSV-2感染的自然抵抗力没有显著变化。此外，用生物免疫调节剂微小棒状杆菌或合成免疫调节剂马来酸酐-二乙烯基醚或脂质体中的阿夫立定对小鼠进行预防性治疗，在89Sr治疗的小鼠和正常小鼠中导致了相当的抵抗力增强。这些数据表明，CD-1小鼠对微生物感染的自然抵抗力和免疫调节剂增强的抵抗力不依赖于Mo、PMN或NK细胞的正常水平。抵抗力的增强可能依赖于活化的组织巨噬细胞（M phi）。与循环白细胞的早期变化相反，直到第30天后，常驻腹膜细胞群体才明显改变。然后淋巴细胞明显减少，M phi逐渐减少；M phi的变化显然是由于与正常小鼠中常驻M phi略有增加相比，89Sr治疗的小鼠中腹膜M phi群体缺乏与年龄相关的增加。CD-1小鼠用89Sr治疗后，PMN数量和NK细胞功能通常在约第50天恢复，随后循环Mo部分恢复，除非给予第二剂89Sr。
