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Leishmaniasis causes high morbidity and mortality in tropical and subtropical areas. Mast cells can be activated by Leishmania or Leishmania products in vitro and in vivo. Several innate immunity mediators, including some released by mast cells, play roles in the outcome of the disease. In this study, we examined whether pharmacological inactivation of mast cells before infection with L. major interferes with the progressive disease in BALB/c mice. The results show that, when mast cells are degranulated before challenge with L. major, susceptible mice become more resistant to infection, as measured by decrease of lesion size and lower parasite loads. Mast cell degranulation reduced IL-4 production. Moreover, mast cells degranulation enhanced mRNA expression for IFN-gamma, inducible nitric oxide, CCL2 and CCL5 in response to infection. Mast cell degranulation also decreased parasite loads in IL-4 KO animals, indicating that mediators other than IL-4 are involved in susceptibility in vivo. Taken together, our results disclose a role for mast cells in the induction of susceptibility to infection. This work contributes to a better understanding of the role of mast cells in Leishmania infection, and suggests a new field of study for strategies to contain the parasite, restricting its dissemination.

The role of adenosine on regulation of the (Na(+)+K(+))ATPase activity present in the Malpighian tubules isolated from Rhodnius prolixus was investigated. Adenosine decreases the (Na(+)+K(+)) ATPase specific activity by 88%, in a dose-dependent manner, with maximal effect at a concentration of 10(-9) M. This effect was mimicked by N(6)-cyclohexyladenosine (CHA) at 10(-8) M, an agonist for A(1) adenosine receptor, and was reversed by 10(-9) M 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an antagonist for A(1) adenosine receptor. On the other hand, 5'-N-ethyl-carboxamide adenosine (NECA), an agonist for A(2) adenosine receptor, used in the range of 10(-9)-10(-5) M, did not change the (Na(+)+K(+))ATPase specific activity. In the same way, 10(-8) M 3, 7-dimethyl-1-propargylxanthine (DMPX), an antagonist for A(2) adenosine receptor, did not modify the inhibitory effect of adenosine. These data suggest that the inhibitory effect of adenosine on the (Na(+)+K(+))ATPase specific activity present in Malpighian tubules from Rhodnius prolixus is mediated by A(1) adenosine receptor activation. Arch., (Copyright 2000 Wiley-Liss, Inc.)