Polynitroxylαα-hemoglobin (PNH) inhibits peroxide and superoxide-mediated neutrophil adherence to human endothelial cells

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Abstract
Experimental hemoglobin-based O2 carriers e.g. cross-linked αα-hemoglobin (αα-Hb), are under investigation as potential blood substitutes. However, some Hb-based products form strong oxidant species in vivo that may cause adverse clinical effects. We report the prototype of a new class of modified Hb-based O2 carrier, polynitroxylated αα-Hb (PNH), which has antioxidant activities that may reduce inflammatory effects mediated by oxidant formation. We compared the effects of αα-Hb and PNH on xanthine oxidase and H2O2-induced neutrophil-endothelial adhesion in vitro. Both peroxide (> 0.1 mM), and superoxide/peroxide generated by xanthine oxidase (XO) (> 10mU/ml) + 0.1 mM xanthine (X), increased endothelial-neutrophil adhesion. At 30 μM, αα-Hb significantly increased X/XO-mediated adhesion, while PNH inhibited peroxide or X/XO induced adhesion, with maximal inhibition at 10 μM PNH. These data indicate that PNH has antioxidant-anti-inflammatory properties that suggest its use as a potentially safer blood substitute in reperfusion injury, stroke, myocardial infarction and other forms of inflammation.