Hestdal K, Jacobsen S E, Ruscetti F W, Dubois C M, Longo D L, Chizzonite R, Oppenheim J J, Keller J R
Biological Response Modifiers, Program Resources, Inc/DynCorp, Inc, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201.
Blood. 1992 Nov 15;80(10):2486-94.
To determine the mechanism(s) by which interleukin-1 (IL-1) promotes granulopoiesis in vivo, we examined the effect of in vivo administration of IL-1 alpha on colony-stimulating factor (CSF) receptor expression on bone marrow cells (BMCs) and whether this directly correlated with progenitor cell responsiveness. Administration of IL-1 alpha to mice induced the upregulation of both granulocyte-macrophage-CSF (GM-CSF) and IL-3 receptors, which reached a maximum 24 hours after IL-1 alpha injection on unfractionated BMCs. This upregulation was more pronounced on the progenitor-enriched cell population (lineage-negative [Lin(-)]). The enhanced GM-CSF and IL-3 receptor expression directly correlated with enhanced IL-3- or GM-CSF-induced growth of colony-forming unit-culture (CFU-c) or CFU-mixture (CFU-Mix; colonies containing macrophages, granulocytes, and erythroid cells). In addition, the absolute number of high proliferative potential-colony-forming cells (HPP-CFC) was increased fivefold. In contrast, granulocyte-CSF (G-CSF)-specific binding on unfractionated BMCs was rapidly (4 hours) reduced after IL-1 alpha administration and returned to control levels by 24 hours. This reduction correlated with IL-1 alpha-induced margination of mature granulocytes (RBC-8C5hi cells), which express high levels of G-CSF receptors. IL-1 alpha treatment did not affect G-CSF receptor expression on Lin- cells. Pretreatment of mice with anti-type I IL-1 receptor antibody blocked the IL-1 alpha-induced upregulation of GM-CSF and IL-3 receptor expression on BMCs. Taken together, as one possible mechanism, IL-1 alpha in vivo may stimulate the expression of functional GM-CSF and IL-3 receptors on BMCs indirectly, and, in concert with the induction of circulating CSF levels, may account for the ability of IL-1 alpha to stimulate hematopoiesis in vivo.
为了确定白细胞介素-1（IL-1）在体内促进粒细胞生成的机制，我们研究了体内给予IL-1α对骨髓细胞（BMC）上集落刺激因子（CSF）受体表达的影响，以及这是否与祖细胞反应性直接相关。给小鼠注射IL-1α可诱导粒细胞-巨噬细胞集落刺激因子（GM-CSF）和IL-3受体上调，在未分离的BMC上，IL-1α注射后24小时达到最大值。这种上调在富含祖细胞的细胞群体（谱系阴性[Lin(-)]）中更为明显。GM-CSF和IL-3受体表达增强与IL-3或GM-CSF诱导的集落形成单位培养（CFU-c）或CFU混合物（CFU-Mix；包含巨噬细胞、粒细胞和红细胞的集落）生长增强直接相关。此外，高增殖潜能集落形成细胞（HPP-CFC）的绝对数量增加了五倍。相比之下，未分离的BMC上粒细胞集落刺激因子（G-CSF）特异性结合在给予IL-1α后迅速（4小时）降低，并在24小时恢复到对照水平。这种降低与IL-1α诱导的成熟粒细胞（RBC-8C5hi细胞）边缘化相关，这些细胞表达高水平的G-CSF受体。IL-1α处理不影响Lin-细胞上的G-CSF受体表达。用抗I型IL-1受体抗体预处理小鼠可阻断IL-1α诱导的BMC上GM-CSF和IL-3受体表达上调。综上所述，作为一种可能的机制，体内IL-1α可能间接刺激BMC上功能性GM-CSF和IL-3受体的表达，并与循环CSF水平的诱导协同作用，这可能解释了IL-1α在体内刺激造血的能力。
