Department of Medical Oncology, Hematology, Immunology, Rheumatology and Pulmology, University Hospital of Tübingen, Tübingen, Germany.
Ann N Y Acad Sci. 2012 Aug;1266:171-8. doi: 10.1111/j.1749-6632.2012.06607.x.
Neutrophil granulocytes represent the first immunologic barrier against invading pathogens, and neutropenia predisposes to infection. However, neutrophils may also cause significant collateral inflammatory damage. Therefore, neutrophil numbers are tightly regulated by an incompletely understood homeostatic feedback loop adjusting the marrow's supply to peripheral needs. Granulocyte colony-stimulating factor (G-CSF) is accepted to be the major determinant of neutrophil production, and G-CSF levels have, soon after its discovery, been described to be inversely correlated with neutrophil counts. A neutrophil sensor, or "neutrostat," has, therefore, been postulated. The prevailing feedback hypothesis was established in adhesion molecule-deficient mice; it includes macrophages and Th17 cells, which determine G-CSF levels in response to the number of peripherally transmigrated, apoptosing neutrophils. Recent work has deepened our understanding of homeostatic regulation of neutrophil granulopoiesis, but there are still inconsistent findings and unresolved questions when it comes to a plausible hypothesis, similar to the feedback control models of red cell or platelet homeostasis.
中性粒细胞是抵御入侵病原体的第一道免疫屏障,而中性粒细胞减少会导致感染。然而,中性粒细胞也可能导致严重的炎症损伤。因此,骨髓对周围组织的供应与外周组织的需求之间的平衡反馈回路对中性粒细胞的数量进行了严格的调节。粒细胞集落刺激因子(G-CSF)被认为是中性粒细胞生成的主要决定因素,并且在其发现后不久,就描述了其水平与中性粒细胞计数呈负相关。因此,提出了中性粒细胞传感器或“neutrostat”的假说。目前占主导地位的反馈假说在黏附分子缺陷型小鼠中建立,其中包括巨噬细胞和 Th17 细胞,它们根据外周迁移、凋亡的中性粒细胞的数量来确定 G-CSF 的水平。最近的研究加深了我们对中性粒细胞生成的稳态调节的理解,但在合理的假说方面仍然存在不一致的发现和未解决的问题,类似于红细胞或血小板稳态的反馈控制模型。