Erythrocytic ATP release in the presence of modified cell-free hemoglobin.
The red blood cell (RBC) has been proposed as an O(2) sensor through a direct link between the desaturation of intracellular hemoglobin (Hb) and ATP release, leading to vasodilation. We hypothesized that the addition of cell-free Hb to the extracellular space provides a supplementary O(2) source that reduces RBC desaturation and, consequently, ATP release. In this study, the saturation of RBC suspensions was lowered by additions of deoxygenated hemoglobin-based oxygen carrier (HBOC) and then assayed for extracellular ATP. When an acellular human Hb intramolecularly cross-linked between alpha subunits (alphaalphaHb, p50 = 33 mmHg) was added to the red cell suspension, ATP production was significantly less than that in the presence of a lower p50 HBOC (Hb cross-linked between beta subunits, betabetaHb, p50 = 8 mmHg). These results provide a potential mechanism for the O(2) affinity of HBOCs to interfere with a vasodilatory signal.
Cole
Russell H
RH
Sangart, Inc., San Diego, CA 92121, United States. russell.cole@gmail.com
Malavalli
Ashok
A
Vandegriff
Kim D
KD
D000255:Adenosine Triphosphate / Q000097:blood*; D001784:Blood Gas Analysis; D004912:Erythrocytes / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism
D006454:Hemoglobins; D000255:Adenosine Triphosphate; D010100:Oxygen