Barthlen W, Zantl N, Pfeffer K, Heidecke C D, Holzmann B, Stadler J
Department of Surgery, Technical University of Munich, Klinikum rechts der Isar, Germany.
Surgery. 1999 Jul;126(1):41-7. doi: 10.1067/msy.1999.99060.
The effects of abdominal sepsis on the regulation of cell turnover in bone marrow and on the function of hematopoietic stem cells were investigated.
In a new mouse model of abdominal sepsis (colon ascendens stent peritonitis [CASP]) the proliferation, apoptosis, and colony-forming capacity of bone marrow cells were determined.
Both experimental peritonitis and sham surgery increased proliferation of bone marrow cells significantly (P < .01). Incubation with granulocyte-macrophage colony-stimulating factor but not granulocyte colony-stimulating factor further augmented proliferation of bone marrow cells from septic mice. In contrast to cell proliferation, bone marrow cell apoptosis was significantly (P < .001) increased in response to CASP but not to sham surgery. CASP surgery and treatment of normal bone marrow cells with lipopolysaccharide, tumor necrosis factor-alpha, interleukin 1 beta, and interferon gamma increased the number of apoptotic cells to a similar extent. Stem cell assays revealed that during the late phase of peritonitis the colony formation by granulocytic-monocytic precursors was increased, whereas mature erythroid colony-forming cells were suppressed. Incubation of normal bone marrow cells with lipopolysaccharide and cytokines showed similar effects.
These results reveal differential effects of experimental peritonitis on various hematopoietic lineages and suggest a potential role of inflammatory mediators for the dysregulation of bone marrow cell function during abdominal sepsis.
研究腹部脓毒症对骨髓细胞更新调节及造血干细胞功能的影响。
在一种新的腹部脓毒症小鼠模型（升结肠支架性腹膜炎[CASP]）中，测定骨髓细胞的增殖、凋亡及集落形成能力。
实验性腹膜炎和假手术均显著增加骨髓细胞增殖（P <.01）。用粒细胞-巨噬细胞集落刺激因子而非粒细胞集落刺激因子孵育可进一步增强脓毒症小鼠骨髓细胞的增殖。与细胞增殖相反，CASP可显著增加骨髓细胞凋亡（P <.001），而假手术则无此作用。CASP手术以及用脂多糖、肿瘤坏死因子-α、白细胞介素1β和干扰素γ处理正常骨髓细胞，均可使凋亡细胞数量增加到相似程度。干细胞分析显示，在腹膜炎后期，粒细胞-单核细胞前体的集落形成增加，而成熟红系集落形成细胞受到抑制。用脂多糖和细胞因子孵育正常骨髓细胞也显示出类似效果。
这些结果揭示了实验性腹膜炎对各种造血谱系的不同影响，并提示炎症介质在腹部脓毒症期间骨髓细胞功能失调中可能发挥作用。
