德国沙里泰医学院日前在最新一期美国《国家科学院学报》上报告说，他们发现免疫系统的巨噬细胞在一天中有自己的“作息”规律。医生可根据这种规律，在一天中药效最佳且副作用最低时让风湿或哮喘患者服药。
免疫系统中的巨噬细胞是身体中的“守卫细胞”，能够认出引发炎症和发烧等生理反应的细菌内毒素的结构，进而分解和吞噬它们。研究人员利用基因技术，用荧光素酶为实验鼠的脾脏、淋巴结和腹膜的巨噬细胞基因做标记，观察受内毒素刺激后巨噬细胞分泌物TNF－a和IL－6的情况。
研究人员发现，插入荧光素酶的巨噬细胞的亮度在一天中随时间波动，这表明巨噬细胞每天的基因活动有特定节奏，并不依赖动物体内系统性的糖皮质激素和脾脏细胞的周期性波动，而且其不同基因的每天活跃时间也不尽相同。
研究人员说，根据巨噬细胞的这种“作息”规律，风湿和哮喘等患者的病痛也会波动。医生可据此针对病情，确定药效最佳且副作用最小的服药时间。(生物谷Bioon.com)
生物谷推荐原始出处：
PNAS December 1, 2009, doi: 10.1073/pnas.0906361106
A circadian clock in macrophages controls inflammatory immune responses
Maren Kellera,1, Jeannine Mazucha,1, Ute Abrahama,b, Gina D. Eoma, Erik D. Herzogb, Hans-Dieter Volkc, Achim Kramera,2 and Bert Maiera
aLaboratory of Chronobiology, Institute for Medical Immunology, and Research Center ImmunoSciences and
cInstitute for Medical Immunology, Charité–Universit?tsmedizin, 10117 Berlin, Germany; and
bWashington University, St. Louis, MO 63130
Time of day-dependent variations of immune system parameters are ubiquitous phenomena in immunology. The circadian clock has been attributed with coordinating these variations on multiple levels; however, their molecular basis is little understood. Here, we systematically investigated the link between the circadian clock and rhythmic immune functions. We show that spleen, lymph nodes, and peritoneal macrophages of mice contain intrinsic circadian clockworks that operate autonomously even ex vivo. These clocks regulate circadian rhythms in inflammatory innate immune functions: Isolated spleen cells stimulated with bacterial endotoxin at different circadian times display circadian rhythms in TNF-α and IL-6 secretion. Interestingly, we found that these rhythms are not driven by systemic glucocorticoid variations nor are they due to the detected circadian fluctuation in the cellular constitution of the spleen. Rather, a local circadian clock operative in splenic macrophages likely governs these oscillations as indicated by endotoxin stimulation experiments in rhythmic primary cell cultures. On the molecular level, we show that >8% of the macrophage transcriptome oscillates in a circadian fashion, including many important regulators for pathogen recognition and cytokine secretion. As such, understanding the cross-talk between the circadian clock and the immune system provides insights into the timing mechanism of physiological and pathophysiological immune functions.
