In a recent letter to the editor by Richard et al,1the 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.

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.
100
2002
1511
2
Venerando
B
Fiorilli
A
Croci
G
et al
Acidic and neutral sialidase in the erythrocyte membrane of type 2 diabetic patients.
Blood.
99
2002
1064
1070
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.
25
1992
41
46
4
Jain
SK
McVie
R
Duett
J
Herbst
JJ
Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes.
Diabetes.
38
1989
1539
1543
5
Traving
C
Schauer
R
Structure, function and metabolism of sialic acids.
Cell Mol Life Sci.
54
1988
1330
1349
6
Low
PS
Interaction of native and denaturated haemoglobins with band 3: consequences for erythrocyte structure and function.
Red Blood Cell Membranes.
Agre
P
Parker
JC
1989
237
260
Marcel Dekker
New York, NY
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.
265
1990
3226
3233
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.
278
1991
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.
84
1987
7368
7372
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.
119
1996
636
647
Sign in via your Institution