TY - JOUR
T1 - Polynitroxyl αα-hemoglobin (PNH) inhibits peroxide and superoxide-mediated neutrophil adherence to human endothelial cells
AU - Okayama, Naotsuka
AU - Park, Jae H.
AU - Coe, Laura
AU - Granger, D. Neil
AU - Ma, Li
AU - Hisa, Carleton J.C.
AU - Alexander, J. Steven
PY - 1999
Y1 - 1999
N2 - Experimental hemoglobin-based O2 carriers e.g. crosslinked 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 (> O.1 mM), and superoxide/peroxide generated by xanthine oxidase (XO) (> 10 mU/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.
AB - Experimental hemoglobin-based O2 carriers e.g. crosslinked 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 (> O.1 mM), and superoxide/peroxide generated by xanthine oxidase (XO) (> 10 mU/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.
KW - Catalase
KW - Nitroxide
KW - Oxidant
KW - Superoxide
UR - http://www.scopus.com/inward/record.url?scp=0032588550&partnerID=8YFLogxK
U2 - 10.1080/10715769900300591
DO - 10.1080/10715769900300591
M3 - Article
C2 - 10489119
AN - SCOPUS:0032588550
SN - 1071-5762
VL - 31
SP - 53
EP - 58
JO - Free Radical Research
JF - Free Radical Research
IS - 1
ER -