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 falciparum culture supernatant or from infected erythrocytes is described. The proteins were present only in preparations rich in P. falciparum nuclear material and were soluble at acid pH and in strongly anionic detergents. Four proteins, of 14-18 kDa were identified as the P. falciparum core histones. N-terminal sequence analysis of the 16 and 18 kDa proteins and of a tryptic fragment of the protein mixture revealed strong homologies with deduced cDNA or protein sequences of histones H2A, H2B, and H3 of P. falciparum and other species. Antibodies raised against the proteins cross-reacted weakly with histones of other species and, on immunofluorescence, localized the proteins to schizont nuclei. Anti-P. falciparum histone antibodies were detected in sera of semi-immune human adults but these antibodies did not react with human histones on a Western blot. The large quantities of P. falciparum histone 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 or histone-antibody complexes may contribute to disease pathology.
Longhurst
H J
HJ
Division of Parasitology, National Institute for Medical Research, London, UK.
Holder
A A
AA
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002467:Cell Nucleus / Q000737:chemistry; D003429:Cross Reactions; D004912:Erythrocytes / Q000737:chemistry / Q000469:parasitology; D006657:Histones / Q000097:blood / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000276:immunology; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D000913:Antibodies, Protozoan; D006657:Histones; D010446:Peptide Fragments