THE HISTONES OF PLASMODIUM-FALCIPARUM - IDENTIFICATION, PURIFICATION AND A POSSIBLE ROLE IN THE PATHOLOGY OF MALARIA

A quick and simple method of purifying the histones from Plasmodium fa lciparum culture supernatant or from infected erythrocytes is describe d. The proteins were present only in preparations rich in P. falciparu m nuclear material and were soluble at acid pH and in strongly anionic detergents. Four proteins, of 14-18 kDa were identified as the P. fal ciparum core histones. N-terminal sequence analysis of the 16 and 18 k Da proteins and of a tryptic fragment of the protein mixture revealed strong homologies with deduced cDNA or protein sequences of histones H 2A, H2B, and H3 of P. falciparum and other species. Antibodies raised against the proteins cross-reacted weakly with histones of other speci es and, on immunofluorescence, localized the proteins to schizont nucl ei. Anti-P. falciparum histone antibodies were detected in sera of sem i-immune human adults but these antibodies did not react with human hi stones on a Western blot. The large quantities of P. falciparum histon e released and the chronic nature of malarial infection, together with the unusually high avidity of histones for ligands found in renal and vascular basement membrane, raise the question of a role for histones in the pathogenesis of malarial infection. We suggest that histones o r histone-antibody complexes may contribute to disease pathology.