Enhanced expression of Fas and FasL modulates apoptosis in the lungs of severe P. falciparum malaria patients with pulmonary edema

• Main Authors: Chuchard Punsawad, Parnpen Viriyavejakul, Chayanee Setthapramote, Sarawoot Palipoch
• Other Authors: Walailak University
• Format: Article
• Published: 2018
• Subjects: Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/36852
• Institution: Mahidol University

Abstract: Apoptosis mediated by Fas/FasL has been implicated in pulmonary disorders. However, little is known about the relationship between Fas and FasL in the process of lung injury during malaria infection. Paraffin-embedded lung tissues from malaria patients were divided into two groups: those with pulmonary edema (PE) and those without pulmonary edema (non-PE). Normal lung tissues were used as the control group. Cellular expression of Fas, FasL, and the markers of apoptotic caspases, including cleaved caspase-3 and cleaved caspase-8 in the lung tissues were investigated by the immunohistochemistry (IHC) method. Semi-quantitative analysis of IHC staining revealed that cellular expression of Fas, FasL, cleaved caspase-8, and cleaved caspase-3 were significantly increased in the lungs of patients with PE compared with the lungs of patients with non-PE and control groups (all P < 0.05). In addition, significant positive correlations were obtained between Fas and apoptosis (rs= 0.937, P < 0.001) and FasL and apoptosis (rs= 0.808, P < 0.001). Significant positive correlations were found between Fas and FasL expression (rs= 0.827, P < 0.001) and between cleaved caspase-8 and cleaved caspase-3 expression (rs= 0.823, P < 0.001), which suggests that Fas-dependent initiator and effector caspases, including cleaved caspase-8 and caspase-3, are necessary for inducing apoptosis in the lungs of patients with severe P. falciparum malaria. The Fas/FasL system and downstream activation of caspases are important mediators of apoptosis and may be involved in the pathogenesis of pulmonary edema in severe P. falciparum malaria patients. The proper regulation of the Fas/FasL pathway can be a potential treatment for pulmonary complications in falciparum malaria patients.