Molecular and Biochemical Parasitology 99 (1999) 269 – 273 Short communication Assay of Schistosoma mansoni calcineurin phosphatase activity and assessment of its role in parasite survival Ayman Khattab 1 , Livia Pica-Mattoccia, Richard Wenger 2 , Donato Cioli, Mo-Quen Klinkert * Institute of Cell Biology, Consiglio Nazionale delle Ricerche, Viale Marx 43, Rome, Italy Received 7 November 1998; received in revised form 11 January 1999; accepted 11 January 1999 Keywords: Schistosoma mansoni ; Calcineurin phosphatase; Inhibition; Cyclosporin A The immunosuppressive drug cyclosporin A (CsA) has been shown to possess unexpected an- tiparasitic activities, notably against schistosomes, plasmodia, cestodes and filariae [1]. In a previous attempt to understand the mechanism of CsA antischistosomal action, we postulated that CsA killed schistosomes by blocking the enzymatic function of cyclophilin (CYP). This hypothesis relied on the identification of CYP as a receptor protein of CsA and was suggested by experimen- tal evidence showing that CsA inhibits schisto- some CYP peptidyl-prolyl-cis -trans -isomerase activity. However, our results did not support the notion that inhibition of CYP activity is the cause of parasite death [2]. In the experiments reported here, we consider an alternative hypothesis, i.e. that the lethal effect of CsA on schistosomes may be linked to the inhibition of the phosphatase activity of calcineu- rin (CN) by the drug-CYP complex. Such a mech- anism is indeed the basis of the immuno- suppressive activity of CsA and of the unrelated drug FK506 [3,4]. Complexes of CsA and FK506 with their respective immunophilin ligands, cy- clophilin (CYP) and FK506 binding protein (FKBP) bind to CN and inhibit its phosphatase activity, preventing dephosphorylation of tran- scription factors. Consequently, early lymphokine genes regulating the immune response are not transcribed [5,6]. Even though CN is particularly abundant in T cells and in the brain, its presence has been * Corresponding author. Present address: Sektion Human- parasitologie, Institut fu ¨ r Tropenmedizin, Universita ¨t Tu ¨ bin- gen, Wilhelmstrasse 27, 72074 Tu ¨ bingen, Germany. Tel.: +49-7071-2980240; fax: +49-7071-295189. 1 Present address: Medical Research Institute, University of Alexandria, Alexandria, Egypt. 2 Present address: Wenger Chemtech, CH-4125 Riehen, Switzerland. 0166-6851/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII:S0166-6851(99)00014-6