title: Band 3 modifications in Plasmodium falciparum-infected AA and CC erythrocytes assayed by autocorrelation analysis using quantum dots.
abstract: The molecular stability of hemoglobin is critical for normal erythrocyte functions, including oxygen transport. Hemoglobin C (HbC) is a mutant hemoglobin that has increased oxidative susceptibility due to an amino acid substitution (beta6: Glu to Lys). The growth of Plasmodium falciparum is abnormal in homozygous CC erythrocytes in vitro, and CC individuals show innate protection against severe P. falciparum malaria. We investigated one possible mechanism of innate protection using a quantum dot technique to compare the distribution of host membrane band 3 molecules in genotypically normal (AA) to CC erythrocytes. The high photostability of quantum dots facilitated the construction of 3D cell images and the quantification of fluorescent signal intensity. Power spectra and 1D autocorrelation analyses showed band 3 clusters on the surface of infected AA and CC erythrocytes. These clusters became larger as the parasites matured and were more abundant in CC erythrocytes. Further, average cluster size (500 nm) in uninfected (native) CC erythrocytes was comparable with that of parasitized AA erythrocytes but was significantly larger (1 microm) in parasitized CC erythrocytes. Increased band 3 clustering may enhance recognition sites for autoantibodies, which could contribute to the protective effect of hemoglobin C against malaria.
authors.affiliation: Biochemical and Biophysical Parasitology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Tokumasu
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.forename: Graciela R
authors.initials: GR
authors.lastname: Ostera
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Brittain
authors.forename: Jeeseong
authors.initials: J
authors.lastname: Hwang
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wellems
authors.forename: James A
authors.initials: JA
authors.lastname: Dvorak
mesh_terms: D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005838:Genotype; D006444:Hemoglobin C / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D007150:Immunohistochemistry; D008288:Malaria / Q000517:prevention & control; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D008962:Models, Theoretical; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D010963:Plasmodium falciparum / Q000378:metabolism*; D045663:Quantum Dots
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000939:Epitopes; D006444:Hemoglobin C; D010100:Oxygen