CHARACTERIZATION OF THE HUMAN SERUM TRYPANOSOME TOXIN, HAPTOGLOBIN-RELATED PROTEIN

Haptoglobin-related protein (HPR) is a serum protein that is > 90% hom ologous to the acute-phase reactant haptoglobin (Hp). Haptoglobin bind s and removes free hemoglobin (Hb) from the circulation, Hpr levels ar e elevated with tumor progression in the serum of some cancer patients , but the relevance of this observation is not understood. HPR is an i ntegral part of two distinct high molecular weight complexes (trypanos ome lytic factor 1 (TLF1) and TLF2) that are lytic for the African par asite Tryanosoma brucei brucei. Previous data indicate that HPR repres ents the toxic component of both trypanosoma lytic factors. It has bee n proposed that after uptake by the parasite, Hb bound to HPR causes l ysis in a peroxidase-dependent process, We report that the molecular a rchitecture of HPR in normal human serum is different from that of Rp and that HPR does not bind Hb in normal human serum. Immunodepletion o f all detectable Hb from TLF1 does not deplete TLF1 of HPR or trypanol ytic activity, suggesting that; the mechanism of parasite lysis is Hb- independent.