Sickle Cells Protect

Abstract

Cell Biology![Figure][1] CREDIT: JANICE HANEY CARR/CDC The genetic mutation that causes sickle cell anemia is a double-edged sword. Individuals who carry one copy of the mutant hemoglobin allele do not develop sickle cell disease but can show greater resistance to malaria. This may be because despite not developing full-blown disease, their blood still carries some consequences of the mutated allele. Ferreira et al. have now analyzed the chain of events that connect the pathology of one copy of mutant hemoglobin with defense against malaria. Mice that express a sickle variant of the human hemoglobin gene were less likely to develop cerebral malaria than normal mice, despite similar parasite loads. The protective effect was attributed to heme oxygenase-1 (HO-1), which metabolizes free heme, generating carbon monoxide as one of the derivatives. In mice with the sickle cell allele, there was a greater tendency for release of free heme, leading to increased induction of HO-1 to remove the heme, which generated more carbon monoxide, which in turn bound to and stabilized hemoglobin, with the overall effect being reduced immune pathology and oxidative stress. Unlike many defense strategies that reduce pathogen burden, this strategy allows the host to be more tolerant of the infection. Cell 145 , 398 (2011). [1]: pending:yes