Degradation of plasmodial antigens by human neutrophil elastase.
Human neutrophil elastase (HNE) has been well-studied with respect to its role in pathologic states, but less is known about the physiologic functions of this important granulocyte enzyme. In the present study, we show that HNE can degrade the major circumsporozoite protein of the infective (sporozoite) stage of Plasmodium vivax malaria, and that this enzyme can also interfere with the cytoadherence of human E infected with Plasmodium falciparum (strain K+ FMG-FCR3) (IE). Cytoadherence reactions are not only blocked by treatment of IE with as little as 10 fg HNE/IE, but already adherent IE are also removed by the enzyme. Normal E surface Ag are not extensively destroyed by these doses of HNE. This suggests that the effect of HNE on cytoadherence is selective and probably due to degradation of the malarial Ag exported to the IE surface and responsible for the formation of "recognition knobs" upon which the cytoadherence reaction depends. This conclusion, in turn, was supported by the results of Western blot analysis showing that HNE degrades a high m.w. Ag found exclusively in membrane extracts of IE. Our results suggest that one physiologic role of HNE may be degradation of parasitic antigens during host defense against malaria.
Janoff
A
A
Department of Pathology, State University of New York, Stony Brook 11794.
Roth
W J
WJ
Sinha
S
S
Barnwell
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000302:isolation & purification / Q000378:metabolism*; D000954:Antigens, Surface / Q000302:isolation & purification / Q000378:metabolism; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology* / Q000469:parasitology; D009842:Oligopeptides / Q000302:isolation & purification; D010196:Pancreatic Elastase / Q000502:physiology*; D010447:Peptide Hydrolases; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins; D011961:Receptors, Fc / Q000187:drug effects; D012091:Repetitive Sequences, Nucleic Acid; D012397:Rosette Formation; D012697:Serine Endopeptidases
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D009842:Oligopeptides; D015800:Protozoan Proteins; D011961:Receptors, Fc; C041595:circumsporozoite protein, Protozoan; D002403:Cathepsins; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase