Role of sialic acid in survival of erythrocytes in the circulation: interaction of neuraminidase-treated and untreated erythrocytes with spleen and liver at the cellular level.

Abstract

Sialidase (neuraminidase; acylneuraminyl hydrolase; EC 3.2.1.18)treated erythrocytes obtained from different species are susceptible to rapid elimination from the circulation and are sequestered in the liver and spleen. The present studies were concerned with the mechanism of this clearance and how it may relate to the normal physiological process of removing senescent erythrocytes from the circulation. The Other investigators have shown (5-8) that the sialic acid content of circulating erythrocytes varies with the age of the erythrocyte. In older erythrocytes sialic acid content is 10-15% less than in younger erythrocytes (6).Autologous transfusion of sialidase-treated erythrocytes results in their rapid disappearance from the circulation. This is true in several different species, such as rats (9, 10), rabbits (4, 10-13), dogs (4), goats (4), and human beings (14). Removal of only 10% of the total sialic acid present on the surface of erythrocytes is sufficient to eliminate these sialidase-treated erythrocytes from the circulation (4). Moreover, the 51Cr label used to tag the sialidase-treated erythrocytes accumulates in the liver (9, 10) and spleep (9).The present studies were concerned with the process by which the sialidase-treated erythrocytes are sequestered in the liver and sp1een. These studies were initiated with the concept that the physiological removal of senescent erythrocytes from the circulation may be analogous to the removal of sialidasetreated erythrocytes. The results of this study demonstrate that sialidase-treated erythrocytes preferentially adhere to Kupffer cells in the liver or to mononuclear cells in the spleen. These investigations correlate well with the histological findings of Schauer (personal communication). MATERIALS AND METHODSMaterials. Sialidase was prepared from Vibrio cholerae as described (3). Clostridium perfringens sialidase was obtained commercially from Sigma Biochemicals (Type VI, lot SOC-8010) and Cl. histolytwum collagenase was purchased from Enzymatic Treatment of Erythrocytes. Blood was collected in EDTA (1.4 mg/ml) from 200-to 250-g male rats (SpragueDawley strain) maintained on standard laboratory chow and tap water ad lib. After anesthetic induction with ethyl ether, the blood was withdrawn by a sterile cardiac puncture. The erythrocytes were treated with sialidase as described (4). The erythrocytes were washed twice in 0.9% saline (pH 7.0) and the buffy coat was removed. After a final wash with 0.83% saline in 10 mM CaCl2, the erythrocytes were incubated at 370 for 30 min with 0.2 unit* of sialidase per ml of packed cells or incubated for 30 min at 370 in CaCl2/saline only. The erythrocytes were then washed three times in saline before further study, and the supernatants were assayed for free sialic acid by the quantitative thiobarbituric acid method (15). The erythrocytes were prepared before the liver or spleen cells because they were stable at 40 for at least 3 hr.Isolation of Rat Liver Hepatocytes and Kupffer Cells. The method is based on that of ...

Sialylation Controls Prion Fate in Vivo

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Evidence for an Asialoglycoprotein Receptor on Nonparenchymal Cells forO-Linked Glycoproteins

“…The mannose/ N-GlcNAc receptor has been described previously as being associated with sinusoidal/Kupffer cells, but no binding has been reported with glycoproteins bearing terminal GalNAcGal residues such as those in BR3-Fc (Ashwell and Harford, 1982). Desialylated erythrocytes have also been shown to bind to a lectin receptor on Kupffer cells with preference for GalNAc (Aminoff et al, 1977;Schlepper-Schä fer et al 1980). The scavenger receptor C-type lectin is associated with endothelial cells, but it has requirement for adjacent terminal Gal and fucose residues and does not bind Gal/GalNAc-terminating glycans unless they form part of a Lewis x -type epitope (Coombs et al, 2005).…”

Are PEGylated liposomes better than conventional liposomes? A special case for vincristine

“…Monosialotetrahexosylganglioside (GM1) is one of the gangliosides whose terminal sialic acid residues might be responsible for the long life span of erythrocytes (Bratosin et al, 1998). This hypothesis is based on the fact that sialidase-treated erythrocytes are rapidly cleared from the bloodstream (Aminoff et al, 1977). Boman et al (1994) demonstrated that vincristine trapped in liposomes containing 10 mol% GM1 with an intraliposomal pH of 2.0 was highly effective against P388 leukemia.…”