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Blood, 1 March 2003, Vol. 101, No. 5, pp. 2071-2071

CORRESPONDENCE

To the editor:

Acidic and neutral sialidase in the erythrocytes of patients with type 2 diabetes: an answer to comments by Richard et al

In a recent letter to the editor by Richard et al,1 the letter authors made some comments about our work published early this year.2 In our study we observed a sharp decrease of neutral sialidase activity on the surface of erythrocytes of diabetic patients, which accounts at the same time for the significant increase (40%) of sialic acid content. At the end of our discussion, we hypothesized that the higher negative charge at the erythrocyte surface due to this increase results in a premature sequestration of diabetic red cells by macrophages, in accordance with the data reported by Mazzanti et al3 and Jain et al.4 Our hypothesis has been criticized by Richard and coworkers because it conflicts with the notion that a reduction of total sialic acid content is responsible for phagocytosis of senescent red cells.

Our thoughts on this matter are as follows: (1) The hypothesis reported by Richard et al has been extensively debated over the years,5 and contrary to what the authors hint, it is not the only one known nor the most accepted, nonetheless it was not in our intentions to discredit it. (2) We believe in the importance of sialic acid in the process of recognition of senescent red cells, but as part of a more complex process, where other molecules are involved, as suggested in other hypotheses.6 Indeed, according to Beppu et al7 and Kannan et al,8 the molecular consequences of the oxidative damage occurring in senescent erythrocytes are likely responsible for their clearance. We think that the reduction of sialic acid content in specific domains of the surface, and not its overall decrease, may trigger the macrophage recognition.9,10 (3) The theory reported by Richard et al is eventually unsuitable to explain our experimental results. In fact, if the overall sialic acid decrease was responsible for senescent erythrocytes recognition, we should have observed an increase in life span of erythrocytes in diabetes mellitus, yet we observed the opposite phenomenon.

In conclusion we would like to emphasize once again that it was not in our intentions to invalidate the role of sialic acid decrease in erythrocyte removal, even though we do believe in a different hypothesis on erythrocytes senescence, at least in diabetic patients.


Bruno Venerando, Amelia Fiorilli, Gianluigi Croci, Cristina Tringali, Giancarlo Goi, Laura Mazzanti, Giovanna Curatola, Giovanni Segalini, Luca Massaccesi, Adriana Lombardo, and Guido Tettamanti
Correspondence: Bruno Venerando, Department of Medical Chemistry and Biotechnology, The Medical School, University of Milan, Via Fratelli Cervi, 93, 20090-Segrate (Milan) Italy; e-mail: bruno.venerando{at}unimi.it

References

1. Richard T, Boudjeltia KZ, Piagnerelli M, Vanhaeverbeek M. Acidic and neutral sialidase in the erythrocytes of patients with Type 2 diabetes: influence on erythrocyte lifespan [letter]. Blood. 2002;100:1511[Free Full Text].

2. Venerando B, Fiorilli A, Croci G, et al. Acidic and neutral sialidase in the erythrocyte membrane of type 2 diabetic patients. Blood. 2002;99:1064-1070[Abstract/Free Full Text].

3. Mazzanti L, Faloia E, Rabini RA, et al. Diabetes mellitus induces red blood cell plasma membrane alterations: possibly affecting the aging process. Clin Biochemistry. 1992;25:41-46.

4. Jain SK, McVie R, Duett J, Herbst JJ. Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes. 1989;38:1539-1543[Abstract].

5. Traving C, Schauer R. Structure, function and metabolism of sialic acids. Cell Mol Life Sci. 1988;54:1330-1349.

6. Low PS. Interaction of native and denaturated haemoglobins with band 3: consequences for erythrocyte structure and function. In: Agre P,Parker JC, eds. Red Blood Cell Membranes. New York, NY: Marcel Dekker; 1989:237-260.

7. Beppu M, Mizukami A, Nagoya M, Kikugawa K. Binding of anti-band3 autoantibody to oxidatively damaged erythrocytes: formation of senescent antigen on erythrocyte surface by an oxidative mechanism. J Biol Chem. 1990;265:3226-3233[Abstract/Free Full Text].

8. Kannan R, Yuan J, Low PS. Isolation and partial characterization of antibody and globin-enriched complexes from membranes of dense human erythrocytes. Biochem J. 1991;278:57-62.

9. Lutz HU, Bussolino F, Flepp R, et al. Naturally occurring anti-band 3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes. Proc Natl Acad Sci U S A. 1987;84:7368-7372[Abstract/Free Full Text].

10. Ando K, Kikugawa K, Beppu M. Binding of anti-band 3 autoantibody to sialylated poly-N-acetyllactosaminyl sugar chains of band3 glycoprotein on polyvinylidene difluoride membrane and sepharose gel: further evidence for anti-band 3 auto antibody binding to the sugar chains of oxidized and senescent erythrocytes. J Biochem. 1996;119:636-647.


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Related Article in Blood Online:

Acidic and neutral sialidase in the erythrocytes of patients with Type 2 diabetes: influence on erythrocyte lifespan
Thibault Richard, Karim Zouaoui Boudjeltia, Michaël Piagnerelli, and Michel Vanhaeverbeek
Blood 2002 100: 1511. [Full Text] [PDF]




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