Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contact tolerance describes an immunological state which is caused by ordinary contact allergens painted in doses too low to sensitize, either once or repeatedly, onto healthy intact skin. The tolerance state accomplished by this means in BALB/c and C57BI/6 mice was found to be mediated by hapten-specific T cells that adoptively transferred tolerance to naive recipients. Furthermore, these cells were shown to be sensitive to cyclophosphamide, to express the Lyt2+ (CD8) phenotype, and to produce, upon restimulation in vitro, predominantly anti-inflammatory cytokines such as IL-4, IL-5 and IL-10. These data indicate that contact tolerance of the low zone type is actively mediated by Th2-like CD8 T cells rather than arising as a consequence of clonal anergy. The induction of contact tolerance appeared to be strictly dose-dependent. As opposed to sensitizing doses of allergen, subsensitizing doses did not involve epidermal Langerhans cells discernibly. This was suggested by their normal ultrastructure, their unaffected adenosine triphosphatase system, the inefficacy of functional blocking and excision experiments. Both radiolabeled and fluorescent contact sensitizers were observed to readily enter the bloodstream, thereby being dispersed throughout the body. Presumably, contact tolerance is induced systemically rather than locally. The presence of hapten-specific tolerance can only be uncovered through a subsequent attempt to sensitize. If the attained sensitization turns out to be significantly lower than that of immunologically naive controls, and if sensitization to chemically unrelated sensitizers is not impaired, hapten-specific tolerance does exist. Thus, contact tolerance is a result obtained from experimental sensitization in animals. Nonetheless, it is assumed to occur also in humans, although it is not demonstrable unless different proofs of existence become available.
 ...
PMID:Contact tolerance. 1072 10

Extracellular ATP and adenosine are important regulators of immune responses; however, contribution of purinergic signaling to host defense during persistent microbial infections remains obscure. Lyme borreliosis is a common arthropod-borne infection caused by Borrelia burgdorferi sensu lato. In this study, we investigated whether lymphoid purinergic signaling contributes to the mechanisms by which borreliae species evade the immune system and trigger joint inflammation. Intracutaneous inoculation of Borrelia garinii to C3H/He mice induced symptomatic infection manifested in elevated levels of borrelia-specific IgG Abs, persistent spirochete dissemination into the tissues and joint swelling, as well as approximately 2- to 2.5-fold enlargement of draining lymph nodes with hyperplasia of B cell follicle area and L-selectin shedding from activated T lymphocytes. Purine catabolism was also activated in lymph nodes but not spleen and blood of infected C3H/He mice within the first 4 postinfection weeks, particularly manifested in transient upregulations of adenosine triphosphatase/ectonucleoside triphosphate diphosphohydrolase and ecto-5'-nucleotidase/CD73 on CD4(+)CD8(+) T lymphocytes and adenosine deaminase activity on B220(+) B lymphocytes. Compared with borrelia-susceptible C3H/He strain, lymphocytes from C57BL/6 mice displayed markedly enhanced adenosine-generating capability due to approximately three times higher ratio of ecto-5'-nucleotidase to adenosine deaminase. Borrelia-infected C57BL/6 mice efficiently eradicated the inoculated spirochetes at more chronic stage without any signs of arthritis. Strikingly, deletion of key adenosine-generating enzyme, ecto-5'-nucleotidase/CD73, was accompanied by significantly enhanced joint swelling in borrelia-infected CD73-deficient C57BL/6 mice. Collectively, these data suggest that insufficient basal adenosine level and/or pathogen-induced disordered lymphoid purine homeostasis may serve as important prerequisite for promotion of inflammatory responses and further host's commitment to persistence of bacterial infection and arthritis development.
 ...
PMID:Disordered lymphoid purine metabolism contributes to the pathogenesis of persistent Borrelia garinii infection in mice. 2035 56