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Blood, Vol. 93 No. 6 (March 15), 1999:
pp. 2121-2127
Structural and Functional Consequences of Antigenic Modulation of Red
Blood Cells With Methoxypoly(Ethylene Glycol)
Kari L. Murad,
Kathleen L. Mahany,
Carlo Brugnara,
Frans A. Kuypers,
John W. Eaton, and
Mark D. Scott
From Albany Medical College, Albany, NY; Children's Hospital,
Boston, MA; Children's Hospital Oakland Research Institute, Oakland,
CA; and Baylor College of Medicine, Houston, TX.
We previously showed that the covalent modification of the red blood
cell (RBC) surface with methoxypoly(ethylene glycol) [mPEG; MW ~5
kD] could significantly attenuate the immunologic recognition of
surface antigens. However, to make these antigenically silent RBC a
clinically viable option, the mPEG-modified RBC must maintain normal
cellular structure and functions. To this end, mPEG-derivatization was
found to have no significant detrimental effects on RBC structure or
function at concentrations that effectively blocked antigenic
recognition of a variety of RBC antigens. Importantly, RBC lysis,
morphology, and hemoglobin oxidation state were unaffected by
mPEG-modification. Furthermore, as shown by functional studies of Band
3, a major site of modification, PEG-binding does not affect protein
function, as evidenced by normal SO4 flux.
Similarly, Na+ and K+ homeostasis were
unaffected. The functional aspects of the mPEG-modified RBC were also
maintained, as evidenced by normal oxygen binding and cellular
deformability. Perhaps most importantly, mPEG-derivatized mouse RBC
showed normal in vivo survival (~50 days) with no sensitization after
repeated transfusions. These data further support the hypothesis that
the covalent attachment of nonimmunogenic materials (eg, mPEG) to
intact RBC may have significant application in transfusion medicine,
especially for the chronically transfused and/or allosensitized patient.
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