The role of CD39 ectonucleotidase in malarial respiratory distress syndrome

Acute Respiratory Distress Syndrome (ARDS) results from acute lung injury (ALI) mainly caused by pulmonary infectious diseases. Breakdown of the alveolar-capillary barrier results in increased vascular permeability, fluid leakage into the interstitial space of the lung, and hypoxia. This picture is reported in pulmonary malaria, in which the cytokine storm occurs and the action of CD8+ T lymphocytes destroys the vascular endothelium. In this context, the hypothesis is that CD39 ectonucleotidase may have an important regulatory role, cleaving ATP released during cell damage and the acute inflammatory response and generating adenosine that has anti-inflammatory activity. As an experimental model, lung disease caused by Plasmodium berghei NK65 will be evaluated in C57BL/6 and ENTPD1-/- mice, as well as in CD8-/- animals adoptively transferred with CD8+ T lymphocytes lacking or lacking this molecule. The parameters to be analyzed will be parasitemia, survival curve, serum concentration of endothelial growth factor (VEGF), pause and respiratory rate, as well as histology, permeability and leukocyte composition of the lungs. The pathogenesis of pulmonary malaria and its immunological mechanisms need to be better understood in order to contribute to the development of target-specific therapies.

Project details

Basic Science

Aug 2022 — Nov 2023

Brazil