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Antigens Protected Functional Red Blood Cells By The Membrane Grafting Of Compact Hyperbranched Polyglycerols
Published on: January 2, 2013
Fine tuning of polymerized pyridoxylated hemoglobin as a red blood cell substitute
1Hemosol Inc., Etobicoke, Ontario, Canada.
Abstract:
Hemoglobin (Hb), modified by pyridoxal 5'-phosphate (PLP) and polymerized by glutaraldehyde (GA) to yield polymerized pyridoxylated Hb (Poly-PLP-Hb), is currently the prime candidate for a hemoglobin-based red cell substitute. However, hematuria and excessive oxygen-binding affinity have been associated with poly-PLP-Hb after transfusion. These phenomena have not yet been explained. In the present communication, we show that pyridoxylation, which is known to reduce the oxygen-binding affinity of Hb to physiological levels, also inhibits the subsequent polymerization of Hb by GA. We attribute poly-PLP-Hb associated hematuria and high oxygen affinity to rapid elimination of these unpolymerized Hb species, leaving in the circulation the polymerized, less-highly pyridoxylated species with excessive oxygen-binding affinity. We proposed a mechanism for PLP inhibition of Hb polymerization, and discuss the implications of our findings for quality control in the preparation of poly PLP-Hb as a red cell substitute.
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