德國沙里泰醫(yī)學(xué)院日前在最新一期美國《國家科學(xué)院學(xué)報》上報告說，他們發(fā)現(xiàn)免疫系統(tǒng)的巨噬細(xì)胞在一天中有自己的“作息”規(guī)律,。醫(yī)生可根據(jù)這種規(guī)律,，在一天中藥效最佳且副作用最低時讓風(fēng)濕或哮喘患者服藥,。
免疫系統(tǒng)中的巨噬細(xì)胞是身體中的“守衛(wèi)細(xì)胞”,，能夠認(rèn)出引發(fā)炎癥和發(fā)燒等生理反應(yīng)的細(xì)菌內(nèi)毒素的結(jié)構(gòu),，進(jìn)而分解和吞噬它們。研究人員利用基因技術(shù),，用熒光素酶為實驗鼠的脾臟,、淋巴結(jié)和腹膜的巨噬細(xì)胞基因做標(biāo)記,，觀察受內(nèi)毒素刺激后巨噬細(xì)胞分泌物TNF－a和IL－6的情況,。
研究人員發(fā)現(xiàn),，插入熒光素酶的巨噬細(xì)胞的亮度在一天中隨時間波動，這表明巨噬細(xì)胞每天的基因活動有特定節(jié)奏,，并不依賴動物體內(nèi)系統(tǒng)性的糖皮質(zhì)激素和脾臟細(xì)胞的周期性波動,，而且其不同基因的每天活躍時間也不盡相同。
研究人員說,，根據(jù)巨噬細(xì)胞的這種“作息”規(guī)律,，風(fēng)濕和哮喘等患者的病痛也會波動。醫(yī)生可據(jù)此針對病情,，確定藥效最佳且副作用最小的服藥時間,。(生物谷Bioon.com)
生物谷推薦原始出處：
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.
