Center for Molecular Immunology and Infectious Disease and the Department of Veterinary and Biomedical Sciences, Penn State University, University Park, PA; Intercollege Graduate Program in Genetics, Penn State University, University Park, PA.
Intercollege Graduate Program in Genetics, Penn State University, University Park, PA.
Exp Hematol. 2020 Sep;89:43-54.e2. doi: 10.1016/j.exphem.2020.07.011. Epub 2020 Aug 2.
Steady-state erythropoiesis generates new erythrocytes at a constant rate, and it has enormous productive capacity. This production is balanced by the removal of senescent erythrocytes by macrophages in the spleen and liver. Erythroid homeostasis is highly regulated to maintain sufficient erythrocytes for efficient oxygen delivery to the tissues, while avoiding viscosity problems associated with overproduction. However, there are times when this constant production of erythrocytes is inhibited or is inadequate; at these times, erythroid output is increased to compensate for the loss of production. In some cases, increased steady-state erythropoiesis can offset the loss of erythrocytes but, in response to inflammation caused by infection or tissue damage, steady-state erythropoiesis is inhibited. To maintain homeostasis under these conditions, an alternative stress erythropoiesis pathway is activated. Emerging data suggest that the bone morphogenetic protein 4 (BMP4)-dependent stress erythropoiesis pathway is integrated into the inflammatory response and generates a bolus of new erythrocytes that maintain homeostasis until steady-state erythropoiesis can resume. In this perspective, we define the mechanisms that generate new erythrocytes when steady-state erythropoiesis is impaired and discuss experimental models to study human stress erythropoiesis.
稳态红细胞生成以恒定的速率产生新的红细胞，并且具有巨大的生产能力。这种生成通过脾脏和肝脏中的巨噬细胞清除衰老的红细胞来平衡。红细胞生成的稳态受到高度调节，以维持足够的红细胞，从而有效地向组织输送氧气，同时避免与过度生成相关的粘度问题。然而，有时红细胞的这种持续生成会受到抑制或不足；在这些时候，红细胞的输出会增加以弥补生产的损失。在某些情况下，增加的稳态红细胞生成可以抵消红细胞的损失，但是，由于感染或组织损伤引起的炎症，稳态红细胞生成会受到抑制。为了在这些条件下维持稳态，激活了替代的应激红细胞生成途径。新出现的数据表明，骨形态发生蛋白 4（BMP4）依赖性应激红细胞生成途径与炎症反应整合在一起，并产生大量新的红细胞，以维持稳态，直到稳态红细胞生成能够恢复。在这个角度来看，我们定义了当稳态红细胞生成受损时产生新红细胞的机制，并讨论了用于研究人类应激红细胞生成的实验模型。
