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Bacterial Neuraminidase-Mediated Erythrocyte Desialylation Provokes Cell Surface Aminophospholipid Exposure

Bacterial Neuraminidase-Mediated Erythrocyte Desialylation Provokes Cell Surface Aminophospholipid Exposure

Syed M Qadri, David A Donkor, Ishac Nazy, Donald R Branch, William P Sheffield

Eur J Haematol. 2018 May;100(5):502-510.

PMID: 29453885

Abstract:

Background:
Surface desialylation is associated with erythrocyte aging and mediates phagocytic recognition and clearance of senescent erythrocytes. Neuraminidases, a family of glycohydrolytic enzymes, cleave the glycosidic linkages between sialic acid and mucopolysaccharides and have previously been implicated in erythrocyte dysfunction associated with sepsis. Erythrocytes in septic patients further display a phenotype of accelerated eryptosis characterized by membrane phospholipid scrambling resulting in phosphatidylserine (PS) externalization. Herein, we examined the impact of artificial erythrocyte desialylation on eryptosis.
Methods:
Using flow cytometry and/or fluorescence microscopy, we analyzed desialylation patterns and eryptotic alterations in erythrocytes exposed to Clostridium perfringens-derived neuraminidase.
Results:
Exogenous bacterial neuraminidase significantly augmented membrane PS exposure and cytosolic Ca2+ levels in a dose- and time-dependent manner. Neuraminidase treatment significantly reduced fluorescence-tagged agglutinin binding, an effect temporally preceding the increase in PS externalization. Neuraminidase-induced PS exposure was significantly curtailed by pretreatment with the pan-sialidase inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid. Neuraminidase treatment further induced hemolysis but did not significantly impact erythrocyte volume, ceramide abundance, or the generation of reactive oxygen species.
Conclusion:
Collectively, our data reveal that alteration of erythrocyte sialylation status by bacterial neuraminidase favors eryptotic cell death, an effect potentially contributing to reduced erythrocyte lifespan and anemia in sepsis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP24967279	N-Acetyl-2,3-dehydro-2-deoxyneuraminic acid		24967-27-9	Price

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