Hemoglobin-Based Blood Substitutes and Enhanced Susceptibility to Bacterial Infections.

摘要

Chemically modified human hemoglobin is currently being studied as a potential blood substitute for use in military and emergency medical applications. We have tested one form of modified hemoglobin, DBBF-HB, against normal Hb in order to determine its ability to promote hemoglobin-driven bacterial infections. Using an experimental model of E. coli peritonitis we have determined that DBBF-HB is equally likely as unmodified Hb (on a mole to mole basis) to lead to a fatal outcome in this model. Further investigations were undertaken to elucidate the molecular mechanism of these hemoglobin-driven bacterial infections. The strains of E. coli that exhibit the hemoglobin-adjuvant effect are resistant to phagocytosis by peritoneal macrophages. This feature may explain why hemoglobin is necessary (nutritional iron) but not sufficient for the promotion of E. coli infections. We are currently examining the composition of the outer membrane proteins in the hemoglobin-adjuvant strains. In addition, using a molecular biological approach, we are attempting to clone the gene(s) responsible for the hemoglobin adjuvant phenotype in E. coli. Further understanding of the mechanism of hemoglobin driven bacterial infections may enable the rational design of a safe blood substitute. Bacterial infections, E. coli infections, Blood substitutes, Hemoglobin-based blood substitutes.