Acidic and neutral sialidase in the erythrocytes of patients with Type 2 diabetes: influence on erythrocyte lifespan

Venerando et al reported an increased quantity of sialic acid at the surface of erythrocytes in diabetic patients and associated the increase with decreased activity of neutral sialidase, an enzyme for which they had previously demonstrated a role in physiologic desialylation of red cells.1 In their discussion they hypothesized that this excess in sialic acid was responsible for a shorter life span of erythrocytes in diabetes mellitus.

This second assertion is in contradiction with what is commonly known about phagocytosis of senescent red cells. Indeed, several lines of evidence support the contrary hypothesis. The mechanism proposed for this selective recognition and uptake of desialylated red cells is that the macrophage recognizes the adjacent galactose group, which is unmasked by desialylation of glycophorin glycans. Several studies support this hypothesis.

First, in vivo studies showed that neuraminidase-treated erythrocytes are sequestrated more quickly by resident macrophages of the spleen, liver, and bone marrow.2,3,4 Their life span is also decreased.2 

Second, centrifugation and lectin recognition studies have showed that older erythrocytes carry less sialic acid residue than younger ones. Moreover, these erythrocytes can be resialylated in vitro, suggesting that the rest of the sialic acid–binding group remains intact. Older red cells can be more resialylated than younger ones.2 

Third, a receptor for galactose residue has been identified at the surface of peritoneal macrophages that are capable of performing erythrophagocytosis in vitro.2,3 5 

Fourth, in vitro studies showed that older erythrocytes are preferentially by murine peritoneal macrophages, a reaction that can be inhibited by lactose, which is used as a competitive inhibitor of galactose recognition.2 

To our knowledge no recent data have invalidated this theory.