Nucleotide and nucleoside involvement in immunomodulation in experimental Chagas disease.

The aim of this study was to evaluate whether Trypanosma cruzi infections cause alterations in the levels of seric purines, which could contribute to host immunomodulation. Twelve mice were divided into two groups identified as control (uninfected) and infected (T. cruzi) groups. The influence of the disease on seric purine levels was verified on day 20 post-infection (PI) by HPLC. Infected mice had circulating trypomastigotes during the experiment, as well as amastigote forms in the heart associated with inflammatory infiltrates. Increases on adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine (ADO), inosine (INO), and uric acid (URIC) levels were observed in the infected animals, while the adenosine monophosphate (AMP) and xanthine (XAN) levels were reduced compared with mice of the control group, indicating a possible impairment on the purinergic system, and consequently, on the immune system during the clinical course of the disease. In summary, the T. cruzi infection alters the seric purine levels, and consequently, modulates the immune system.

Immunomodulatory effect of the purine nucleoside inosine following spinal cord contusion injury in rat.

STUDY DESIGN: In vivo study using a moderate spinal cord contusion injury (SCI) model in adult rat. OBJECTIVE: To assess the immunomodulatory effects of the purine nucleoside inosine on macrophage/microglia activation at and near the lesion site and in white matter areas remote from the injury epicenter. SETTING: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY, USA. METHODS: Animals (N=56) were injured using a moderate SCI at T9-T10 spinal level and were divided into three groups, depending on treatment paradigm. Rats received either intraperitoneal or subcutaneous injections of inosine (N=28) or vehicle (N=28). Spinal cord tissue was processed for ED-1 immunoreactivity and the volume fraction of ED-1(+) profiles was calculated using the Cavalieri method and unbiased stereology. RESULTS: The volume fraction of ED-1(+) profiles within gray and lateral white matter regions at and around the lesion site was significantly reduced only following a twice daily-6 week treatment course, compared with vehicle controls, and white matter areas remote from the lesion were unaffected by all inosine treatment paradigms. CONCLUSIONS: Continued subcutaneous delivery of inosine, beginning 15-min post-SCI and persisting throughout the survival period of 6 weeks exerted immunomodulatory effects at and around the lesion site.

The role of the epitope density and cross-reactivity between two different purine nucleosides coupled to cells.

Cellular immune responses against nucleic acid antigens were analyzed in BALB/C mice. Delayed-type hypersensitivity (DTH) could be elicited by immunizing and challenging with either guanosine-coupled spleen cells (G-SC) or adenosine-coupled spleen cells (A-SC), and measured by footpad swellings. The epitope density was critical for immunization. This cellular reaction was specific to nucleosides, and cross-immunity was observed between A-SC and G-SC. In addition, cross-unresponsiveness was observed between these two nucleosides. In contrast, soluble carrier proteins coupled with either guanosine or adenosine did not induce cross-reactive immunity or unresponsiveness. The significance of the difference between these two forms of antigens in the ability to induce cross-reactivity is discussed in the context of T versus B-cell recognition in the induction or the expression of the immune response.