NITRIC-OXIDE INHIBITS ESTABLISHMENT OF MACROSCHIZONT-INFECTED CELL-LINES AND IS PRODUCED BY MACROPHAGES OF CALVES UNDERGOING BOVINE TROPICAL THEILERIOSIS OR EAST-COAST FEVER

Nitric oxide (NO) was produced when bovine peripheral blood mononuclea r cells (PBMC) or purified, adherent PBMC (macrophages) were incubated in vitro with bovine recombinant interferon gamma (Bo rIFN-gamma). NO was produced by cells from naive, uninfected calves as well as by cel ls from cattle either infected with or recovered from infection with T heileria annulata or Theileria parva. PBMC of cattle undergoing tropic al theileriosis (T. annulata infection) or East Coast fever (T. parva infection) synthesized NO spontaneously in vitro. NO was also induced when PBMC of immune, but not of naive, cattle were cultured with T. an nulata macroschizant-infected cell lines. Macrophages alone were not s timulated to produce NO by such infected cells. In vitro establishment of macroschizont-infected cell lines was suppressed either by incubat ing sporozoites with S-nitroso-N-acetyl-DL-penicillamine (SNAP), a NO releasing molecule, prior to invasion of PBMC or by pulsing developing cultures of trophozoite-infected cells with SNAP. Proliferation of es tablished macroschizont-infected cell lines was not affected by SNAP. Taken together with the well documented roles of NO in neutrotransmiss ion, vasodilatation, cell and tissue damage and immunosuppression, the results presented here indicate that NO may not only protect cattle a gainst T. annulata and T. parva but, if produced in excess, play a pro minent role in the pathogenesis of tropical theileriosis and East Coas t fever.