Abstract
BackgroundMalaria-triggered lung injury can occur in both severe and non-severe cases. Platelets may interact with parasitized erythrocytes, leukocytes and endothelium. These interactions can lead to microvessel obstructions and induce release of inflammatory mediators. Induction of the haem oxygenase enzyme is important in the host’s response to free haem and to several other molecules generated by infectious or non-infectious diseases. In addition, an important role for the haem oxygenase-1 isotype has been demonstrated in experimental cerebral malaria and in clinical cases. Therefore, the present work aims to determine the influence of haem oxygenase in thrombocytopaenia and acute pulmonary injury during infection with Plasmodium berghei strain NK65.MethodsC57BL/6 mice were infected with P. berghei and analysed 7-10 days post-infection. For each experiment, Cobalt Protoporphyrin IX/CoPPIX or saline were administered. Bronchoalveolar lavage fluid was used for total and differential leukocyte count and for protein measurement. Lungs were used for histological analyses or for analysis of cytokines and western blotting. The lung permeability was analysed by Evans blue dye concentration. Platelet-leukocyte aggregate formation was assayed using the flow cytometer.ResultsPlasmodium berghei NK65 infection generated an intense lung injury, with increased levels of inflammatory mediators, oedema, and cell migration into the lung. Plasmodium berghei infection was also accompanied by marked thrombocytopaenia and formation of platelet-leukocyte aggregates in peripheral blood. Treatment with the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) modified the inflammatory response but did not affect the evolution of parasitaemia. Animals treated with CoPPIX showed an improvement in lung injury, with decreased inflammatory infiltrate in the lung parenchyma, oedema and reduced thrombocytopaenia.ConclusionData here presented suggest that treatment with CoPPIX inducer leads to less severe pulmonary lung injury and thrombocytopaenia during malaria infection, thus increasing animal survival.
Highlights
IntroductionPlatelets may interact with parasitized erythrocytes, leukocytes and endothelium
Malaria-triggered lung injury can occur in both severe and non-severe cases
Regarding lung injury triggered by infection with P. berghei strain NK65, it has been noted that von Willebrand factor (VWF—a glycoprotein synthesized in endothelial cells and megakaryocytes, what is crucial in normal haemostasis and thromboinflammation), contributed to increased alveolar leakage and VWF deficiency was associated with elevated parasite load, anaemia, and shortened survival time [31]
Summary
Platelets may interact with parasitized erythrocytes, leukocytes and endothelium These interactions can lead to microvessel obstructions and induce release of inflammatory mediators. The non-specificity of these symptoms leads to a delay in seeking medical attention and to delayed diagnosis and treatment. This scenario is a recipt to serious clinical complications of the disease, such as metabolic acidosis (mainly respiratory distress), malaria associated acute respiratory distress syndrome (MA-ARDS), cerebral malaria (MC) and severe malaria anaemia (SMA) [2]. Pulmonary oedema is triggered by increased permeability of the alveolar-capillary membrane, leading to loss of intravascular fluid, with accumulation of macrophages followed by intravascular inflammatory response. The immune response generated in the lung can lead to airway obstruction [4,5,6,7]
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