Progress in the biology of myo-inositol hexakisphosphate (InsP(6)) has been delayed by the lack of a quantitative description of its multiple interactions with divalent cations. Our recent initial description of these [J. Torres, S. Dominguez, M.F. Cerda, G. Obal, A. Mederos, R.F. Irvine, A. Diaz, C. Kremer, J. Inorg. Biochem. 99 (2005) 828-840] predicted that under cytosolic/nuclear conditions, protein-free soluble InsP(6) occurs as Mg(5)(H(2)L), a neutral complex that exists thanks to a significant, but undefined, window of solubility displayed by solid Mg(5)(H(2)L).22H(2)O (L is fully deprotonated InsP(6)). Here we complete the description of the InsP(6)-Mg(2+)-Ca(2+) system, defining the solubilities of the Mg(2+) and Ca(2+) (Ca(5)(H(2)L).16H(2)O) solids in terms of K(s0)=[M(2+)](5)[H(2)L(10-)], with pK(s0)=32.93 for M=Mg and pK(s0)=39.3 for M=Ca. The concentration of soluble Mg(5)(H(2)L) at 37 degrees C and I=0.15M NaClO(4) is limited to 49muM, yet InsP(6) in mammalian cells may reach 100muM. Any cytosolic/nuclear InsP(6) in excess of 49muM must be protein- or membrane-bound, or as solid Mg(5)(H(2)L).22H(2)O, and any extracellular InsP(6) (e.g. in plasma) is surely protein-bound.

Hydatid disease, which affects humans and various livestock species, is caused by the larval stages of the cestode parasite Echinococcus granulosus. The disease involves the growth of a fluid-filled cyst in the host's internal organs. The hydatid cyst wall is generally thought to preclude the access of host immune cells to the cyst, while allowing passage of macromolecules. Thus, evasion of humoral effector mechanisms, in particular the complement system, may be crucial to parasite survival. Evasion of complement might involve inhibition of the C3b deposition step, which can in principle be achieved through parasite-derived or host-derived and parasite-bound regulatory molecules. In this work, extracts from bovine hydatid cysts were analyzed for the presence of factor H-like function, namely the cofactor activity for the breakdown of amidated bovine C3 by bovine factor I. Both this activity and antigenically detectable bovine factor H were found in most extracts. The cofactor activity was retained by an anti-bovine factor H Ab column; as no factor H-cross-reactive parasite molecules were detected in the active extracts, the activity was indeed due to host factor H. The pattern of extraction of host factor H from the parasite tissue indicated that at least part of it was selectively bound to the cyst wall, and that a strong charge component was involved in the binding. Our results indicate that the selective concentration of host factor H from plasma/interstitial fluid may contribute to complement evasion by E. granulosus.