Polynitroxyl alphaalpha-hemoglobin (PNH) inhibits peroxide and superoxide-mediated neutrophil adherence to human endothelial cells.
Experimental hemoglobin-based O2 carriers e.g. cross-linked alphaalpha-hemoglobin (alphaalpha-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 alphaalpha-Hb (PNH), which has antioxidant activities that may reduce inflammatory effects mediated by oxidant formation. We compared the effects of alphaalpha-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) (> 10 mU/ml) + 0.1 mM xanthine (X), increased endothelial-neutrophil adhesion. At 30 microM, alphaalpha-Hb significantly increased X/XO-mediated adhesion, while PNH inhibited peroxide or X/XO induced adhesion, with maximal inhibition at 10 microM 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.
Okayama
N
N
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Park
J H
JH
Coe
L
L
Granger
D N
DN
Ma
L
L
Hisa
C J
CJ
Alexander
J S
JS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001802:Blood Substitutes / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D013481:Superoxides / Q000494:pharmacology*; D014471:Umbilical Veins; D019820:Xanthine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001802:Blood Substitutes; D006454:Hemoglobins; D009589:Nitrogen Oxides; C121926:polynitroxyl hemoglobin; D013481:Superoxides; D019820:Xanthine; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase