Oishi Katsutaka, Ohkura Naoki, Kadota Koji, Kasamatsu Manami, Shibusawa Kentaro, Matsuda Juzo, Machida Kazuhiko, Horie Shuichi, Ishida Norio
Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
J Circadian Rhythms. 2006 Oct 2;4:13. doi: 10.1186/1740-3391-4-13.
Although the number of circulating immune cells is subject to high-amplitude circadian rhythms, the underlying mechanisms are not fully understood.
To determine whether intact CLOCK protein is required for the circadian changes in peripheral blood cells, we examined circulating white (WBC) and red (RBC) blood cells in homozygous Clock mutant mice.
Daytime increases in total WBC and lymphocytes were suppressed and slightly phase-delayed along with plasma corticosterone levels in Clock mutant mice. The peak RBC rhythm was significantly reduced and phase-advanced in the Clock mutants. Anatomical examination revealed hemoglobin-rich, swollen red spleens in Clock mutant mice, suggesting RBC accumulation.
Our results suggest that endogenous clock-regulated circadian corticosterone secretion from the adrenal gland is involved in the effect of a Clock mutation on daily profiles of circulating WBC. However, intact CLOCK seems unnecessary for generating the rhythm of corticosterone secretion in mice. Our results also suggest that CLOCK is involved in discharge of RBC from the spleen.
尽管循环免疫细胞的数量呈现高振幅昼夜节律，但其潜在机制尚未完全明确。
为了确定完整的生物钟蛋白对于外周血细胞昼夜变化是否必要，我们检测了纯合生物钟突变小鼠的循环白细胞（WBC）和红细胞（RBC）。
在生物钟突变小鼠中，白细胞总数和淋巴细胞的日间增加受到抑制，且与血浆皮质酮水平一起稍有相位延迟。红细胞节律峰值在生物钟突变小鼠中显著降低且相位提前。解剖学检查发现生物钟突变小鼠的脾脏呈富含血红蛋白的肿胀红色，提示红细胞积聚。
我们的结果表明，肾上腺内源性生物钟调节的昼夜皮质酮分泌参与了生物钟突变对循环白细胞每日变化的影响。然而，完整的生物钟对于小鼠皮质酮分泌节律的产生似乎并非必要。我们的结果还表明，生物钟参与了红细胞从脾脏的释放。
