Trypanosomes, like many protozoan parasites, are unable to synthesize purines and must rely on the host to provide those compounds. The demand placed on the host's pool of free purines by a rapidly-growing population of extracellular, bloodstream trypanosomes (such as the rodent or African trypanosomes) may have one of two effects, either: (a) marked mobilizaton of purines from tissue sites into the bloodstream, or (b) serious depletion of the normal, circulating concentrations of purines. In either case, the available evidence suggests that significant alterations of the normal properties and functions of host cells that display surface adenosine receptors would result (especially lymphocytes, neutrophils, macrophages and platelets). The goals of this research are to investigate changes in bloodstream purine concentrations and changes in the properties and functions of selected host cells during the course of murine infections with Trypanosoma musculi. The concentrations of 16 purines in the plasma will be determined (by high performance liquid chromatography) at intervals during the course of infection, and subsequent recovery, of two strains of mice (one, C3H, that is particularly susceptible to T. musculi and another, C57Bl/6, that is considerably less susceptible). The marked (3-5 fold) rise in splenocyte activity of the enzymes, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP), which recently has been discovered in trypanosome-infected mice will be studied in detail. Specifically it will be determined: (a) whether or not the stimulation of these enzymes results from an excess or a paucity of purines in the bloodstream, (b) which types of splenic cells display the elevated enzyme activities, (c) whether or not the stimulus comes from direct action of the parasites (or parasite-derived substances) on cells in which the enzyme activity increases or is mediated indirectly through another type of host cell, and (d) whether or not the elevated enzyme levels are associated with depressed capability of infected hosts to generate immune responses. Finally, once it is known how the bloodstream concentrations of purines change during infection, the effects of similar changes in the properties and functions of selected cells (B-lymphocytes, T-lymphocytes, neutrophils, Kupffer cells and platelets) maintained in vitro will be explored. These studies will provide insight concerning the mechanisms through which trypanosome-mediated alterations in host purine concentrations result in altered cellular activities, and may help to explain the success of trypanosomes in resisting the immune responses of their hosts.
