Red Blood Cell Clearance in Inflammation

Abstract

Anemia is a frequently encountered problem in the critically ill patient. The inability to compensate for anemia includes several mechanisms, collectively referred to as anemia of inflammation: reduced production of erythropoietin, impaired bone marrow response to erythropoietin, reduced iron availability, and increased red blood cell (RBC) clearance. This review focuses on mechanisms of RBC clearance during inflammation. We state that phosphatidylserine (PS) expression in inflammation is mainly enhanced due to an increase in ceramide, caused by an increase in sphingomyelinase activity due to either platelet activating factor, tumor necrosis factorα, or direct production by bacteria. Phagocytosis of RBCs during inflammation is mediated via RBC membrane protein band 3. Reduced deformability of RBCs seems an important feature in inflammation, also mediated by band 3 as well as by nitric oxide, reactive oxygen species, and sialic acid residues. Also, adherence of RBCs to the endothelium is increased during inflammation, most likely due to increased expression of endothelial adhesion molecules as well as PS on the RBC membrane, in combination with decreased capillary blood flow. Thereby, clearance of RBCs during inflammation shows similarities to clearance of senescent RBCs, but also has distinct entities, including increased adhesion to the endothelium.

Synergistic effect of <i>Elephantopus scaber</i> L and <i>Sauropus androgynus</i> L merr extracts in modulating prolactin hormone and erythropoiesis in pregnant typhoid mice

“…Inflammation caused by bacteria can reduce EPO production and iron availability [15]. Reduction of EPO levels leads to reduced maturation of erythrocyte precursors.…”

“…The reduced iron availability results in hepcidin activation during inflammation. Hepcidin is a major regulator of iron that binds to the iron exporter ferroportin, causing internalization of iron and inhibiting its release [15]. Reduced EPO production and iron availability lead to anemia, and during pregnancy this can result in pre-term labor, pre-eclampsia, and sepsis [16].…”

“…S. androgynus acts as a secondary messenger in cell signal transduction of hormones and growth factors. Increasing prolactin indirectly increases the number of erythrocytes [15]. Prolonged administration of prolactin increases the red blood cell mass in normal mice [6].…”

Erythrocyte Sodium Sensitivity and Eryptosis in Chronic Hemodialysis Patients

“…In addition, we excluded patients with catheter as dialysis access. Patients with catheters are more prone to inflammatory processes, which in turn correlate positively with eryptosis [64, 65]. …”

The HIF System Response to ESA Therapy in CKD‐Anemia

“…The activation of inflammatory cells is also associated with increased oxidative stress, favoring alterations in red blood cells (RBC) membrane, namely increased phosphatidylserine exposure, increased membrane bound Hb and increased membrane protein band 3 aggregation, all markers for RBC phagocytosis by macrophages and, thus, for a premature RBC removal [83,84]. Uremic toxins and pro-inflammatory cytokines also inhibit erythropoiesis, through the inhibitory effect of IL-1β, TNF-α and IFN-γ on early erythroid cell stages in the bone marrow [85].…”