期刊
CELLULAR MICROBIOLOGY
卷 13, 期 9, 页码 1410-1428出版社
WILEY
DOI: 10.1111/j.1462-5822.2011.01630.x
关键词
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资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil (CNPq)
- Programa de Nucleos de Excelencia (PRONEX)
- Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Instituto Nacional de Ciencia e Tecnologia para Pesquisa Translacional em Saude e Ambiente na Regiao Amazonica (INPeTAm/UFRJ)
Nucleotides are released into the extracellular milieu from infected cells and cells at inflammatory sites. The extracellular nucleotides bind to specific purinergic (P2) receptors and thereby induce a variety of cellular responses including antiparasitic effects. Here we investigated whether extracellular nucleotides affect leishmanial infection in macrophages, and found that UTP reduces strongly the parasite load in peritoneal macrophages. Ultrastructural analysis of infected cells revealed that UTP induced morphological damage in the intracellular parasites. Uridine nucleotides also induced dose-dependent apoptosis of macrophages and production of ROI and RNI only in infected macrophages. The intracellular calcium measurements of infected cells showed that the response to UTP, but not UDP, increased the sensitivity and amplitude of cytosolic Ca2+ changes. Infection of macrophages with Leishmania upregulated the expression of P2Y(2) and P2Y(4) receptor mRNA. The data suggest indirectly that Leishmania amazonensis infection induces modulation and heteromerization of P2Y receptors on macrophages. Thus UTP modulates the host response against L. amazonensis infection. UTP and UTP homologues should therefore be considered as novel components of therapeutic strategies against cutaneous leishmaniasis.
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