The oxidative effect of bacterial lipopolysaccharide on native and cross-linked human hemoglobin as a function of the structure of the lipopolysaccharide.
The binding of lipopolysaccharide (LPS, also known as bacterial endotoxin) to human hemoglobin is known to result in oxidation of hemoglobin to methemoglobin and hemichrome. We have investigated the effects of the LPSs from smooth and rough Escherichia coli and Salmonella minnesota on the rate of oxidation of native oxyhemoglobin A0 and hemoglobin cross-linked between the alpha-99 lysines. For cross-linked hemoglobin, both smooth LPSs produced a rate of oxidation faster than the corresponding rough LPSs, indicating the importance of the binding of LPS to the hemoglobin. The effect of the LPS appeared to be largely on the initial fast phase of the oxidation reaction, suggesting modification of the heme pocket of the alpha chains. For hemoglobin A0, the rates of oxidation produced by rough and smooth LPSs were very similar, suggesting the possibility that the effect of the LPSs was to cause dissociation of hemoglobin into dimers. The participation of cupric ion in the oxidation process was demonstrated in most cases. In contrast, the rate of oxidation of cross-linked hemoglobin by the LPSs of both the rough and smooth E. coli was not affected by the presence of chelators, suggesting that cupric ion had previously bound to these LPSs. Overall, these data suggest that the physiological effectiveness of hemoglobin solutions now being developed for clinical use may be decreased by the presence of lipopolysaccharide in the circulation of recipients.
Currell
Douglas L
DL
Department of Laboratory Medicine, University of California School of Medicine and Veterans Administration Medical Center, San Francisco, CA 94121, USA.
Levin
Jack
J
D004492:Edetic Acid / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000494:pharmacology; D012475:Salmonella / Q000378:metabolism; D013329:Structure-Activity Relationship
D006454:Hemoglobins; D008070:Lipopolysaccharides; D010618:Phenanthrolines; C002701:neocuproine; D004492:Edetic Acid