Serum xanthine oxidase: origin, regulation, and contribution to control of trypanosome parasitemia.
African trypanosomiasis is caused by Salivarian trypanosomes, tsetse fly-transmitted protozoa that inhabit the blood plasma, lymph and interstitial fluids, and, in the case of Trypanosoma brucei species, also the cerebrospinal fluid of mammal hosts. Trypanosomiasis in people and domestic animals manifests as recurring waves of parasites in the blood and is typically fatal. In contrast, trypanosomiasis in Cape buffaloes, which are naturally selected to resist the disease, is characterized by the development of only one or a few waves of parasitemia, after which the infection becomes cryptic, being maintained by the presence of 1-20 mammal-infective organisms/ml of blood. The control of the acute phase of parasitemia in Cape buffaloes correlates with a decline in blood catalase activity and the generation of trypanocidal H(2)O(2) in serum during the catabolism of endogenous purine by xanthine oxidase. Here we review features of this response, and of trypanosome metabolism, that facilitate H(2)O(2)-mediated killing of the parasites with minimal damage to the host. We also discuss the origin and regulation of serum xanthine oxidase and catalase, and show how recovery of serum catalase in infected Cape buffaloes precludes a role for H(2)O(2) in the long-term, stable suppression of trypanosome parasitemia.
Wang
Jun
J
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Van Praagh
Andrew
A
Hamilton
Erika
E
Wang
Qin
Q
Zou
Baixiang
B
Muranjan
Madhavi
M
Murphy
Noel B
NB
Black
Samuel J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D002020:Buffaloes; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid; D014345:Trypanosoma / Q000502:physiology*; D014352:Trypanosomiasis / Q000469:parasitology*; D014969:Xanthine Oxidase / Q000097:blood*
D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D005947:Glucose; D010100:Oxygen