Metastasis of Theileria annulata macroschizont-infected cells in scid mice is mediated by matrix metalloproteinases.
Theileria annulata (Ta)-infected leucocytes are able to disseminate in scid mice. The dose of virulent parasites of the Ta-Ode line required to achieve quantifiable dissemination was found to be 2 x 10(6) cells given i.p. Dissemination was higher on day 11 post-inoculation than on day 18. The attenuated Ta-Ode cells were found to disseminate very poorly compared to their virulent progenitors, which correlates with a marked reduction in matrix metalloproteinase (MMP) expression. A daily i.p. injection of mice with BB94, a synthetic inhibitor of MMPs, almost completely ablated dissemination compared to controls. This provides strong evidence that metastasis of Theileria annulata macroschizont-infected host cells is mediated by host MMPs induced by the parasite. This has important implications for explaining a number of pathological features of tropical theileriosis in cattle.
Somerville
R P
RP
Department of Biology, University of York, UK.
Adamson
R E
RE
Brown
C G
CG
Hall
F R
FR
D000818:Animals; D002417:Cattle; D002452:Cell Count; D005260:Female; D007668:Kidney / Q000469:parasitology; D007962:Leukocytes / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D008168:Lung / Q000469:parasitology; D008643:Mesentery / Q000469:parasitology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID / Q000469:parasitology*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013154:Spleen / Q000469:parasitology; D016796:Theileria annulata / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D013801:Theileriasis / Q000201:enzymology* / Q000469:parasitology; D013876:Thiophenes / Q000494:pharmacology; D013997:Time Factors; D014774:Virulence
D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D008666:Metalloendopeptidases