Stress Erythropoiesis is a Key Inflammatory Response

Abstract

Bone marrow medullary erythropoiesis is primarily homeostatic. It produces new erythrocytes at a constant rate, which is balanced by the turnover of senescent erythrocytes by macrophages in the spleen. Despite the enormous capacity of the bone marrow to produce erythrocytes, there are times when it is unable to keep pace with erythroid demand. At these times stress erythropoiesis predominates. Stress erythropoiesis generates a large bolus of new erythrocytes to maintain homeostasis until steady state erythropoiesis can resume. In this review, we outline the mechanistic differences between stress erythropoiesis and steady state erythropoiesis and show that their responses to inflammation are complementary. We propose a new hypothesis that stress erythropoiesis is induced by inflammation and plays a key role in maintaining erythroid homeostasis during inflammatory responses.

Stress erythropoiesis in atherogenic mice

“…The earliest committed erythroid progenitors identified ex vivo are the BFU-E and the further differentiated CFU-E, two populations of cells with modifiable self-renewal, proliferation and differentiation capabilities (reviewed in 57 ). Stress erythropoiesis increases BFU-E and CFU-E in the spleen 12 , 17 , 24 . We carried out erythroid-colony forming assays with hypotonic lysed splenocytes and BM cells from ApoE −/− mice fed a WD and ApoE +/+ mice fed a CD.…”

“…To alleviate this inflammatory anemia, the spleen assumes the main erythropoietic role, and stress erythropoiesis is induced in order to meet the oxygen demand in the organism. In chronic inflammatory processes periodic waves of stress erythropoiesis occur 24 – 26 .…”

“…Splenic stress erythropoiesis is dependent on the migration capacity of HSPC to the spleen where the amplification of the erythropoietic cell lineage takes place. The mechanisms involved in this process are not totally coincident with those implicated in steady state erythropoiesis (reviewed in 12 , 24 ). In agreement with previous reports 41 , 42 , we show here an increased number of splenic ST-HSC in atherogenic mice.…”

“…In response to infections, the BM cell differentiation is rapidly biased towards the myeloid branch in detriment of erythropoiesis 18 , 19 along with increased levels of erythroblast apoptosis and the subsequent clearance of the apoptotic corpses (erythrophagocytosis) 20 – 23 . This decrease in the input of mature RBC generated in BM is compensated by splenic stress erythropoiesis (reviewed in 23 , 24 ). In chronic inflammatory diseases the strategy to mitigate inflammatory anemia is the periodic increase of stress erythropoiesis in spleen 24 – 26 .…”

“…This decrease in the input of mature RBC generated in BM is compensated by splenic stress erythropoiesis (reviewed in 23 , 24 ). In chronic inflammatory diseases the strategy to mitigate inflammatory anemia is the periodic increase of stress erythropoiesis in spleen 24 – 26 .…”