Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

Dominik J. Schaer; Paul W. Buehler

doi:10.1101/cshperspect.a013433

Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

Dominik J. Schaer1,2,3 and
Paul W. Buehler4

¹Division of Internal Medicine, University Hospital, Zurich CH-8091, Switzerland
²Center of Integrative Human Physiology University of Zurich, Zurich CH-8057, Switzerland
³Center of Evolutionary Medicine, University of Zurich, Zurich CH-8057, Switzerland
⁴Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Correspondence: dominik.schaer{at}usz.ch; paul.buehler{at}fda.hhs.gov

Abstract

Hemoglobin (Hb) has multiple pathophysiologic effects when released into the intravascular space during hemolysis. The extracellular effects of Hb have resulted in novel models of toxicity, which help to explain endothelial dysfunction and cardiovascular complications that accompany genetic hemolytic anemias, malaria, blood transfusion, and atherosclerosis. The majority of models focus on nitric oxide (NO) depletion; however, in local tissue environments, Hb can also act as a pro-oxidant and inflammatory agent. This can alter cellular differentiation with the potential to deviate immune responses. The understanding of these mechanisms set in the context of natural scavenger and detoxification systems may accelerate the development of novel treatment strategies.