Publication Date:
2011-11-18
Description:
Abstract 2135 Circulating heme is scavenged by multiple plasma proteins and delivered to the liver for degradation. We have recently demonstrated that heme scavenging is variably impaired in transgenic mice with sickle cell disease (SCD). In this study, we tested the hypothesis that excess protein-free plasma heme (PFPH) in the blood circulation, and excess scavenged protein-bound plasma heme (PBPH) destined for degradation cause different types of organ damage in SCD. Transgenic mice expressing exclusively human sickle hemoglobin (SS) were intravenously injected with a dose of heme (25 micromoles/kg) to elevate PBPH only, or with a dose (70 micromoles/kg) sufficient to raise PFPH. In agreement with our previous findings, PFPH was associated with severe lung injury and 100% lethality within 2 hours. This phenomenon occurred independent of any liver involvement. Modest elevation of circulating heme sufficient to raise PBPH only, increased alanine aminotransferase and aspartate aminotranferase 3- to 4-fold (P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine