PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation
| Autor: | Julian L. Goggi, Carla Claser, Boominathan Ramasamy, Peng Wen Tan, Husaini Abdul Rahman, Zi Wei Chang, Siddesh V. Hartimath, Jun Rong Tang, Laurent Rénia, Edward G. Robins, Samantha Yee Teng Nguee, Peter Cheng, Pei Xiang Hor |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Plasmodium berghei 030231 tropical medicine Immunology Inflammation Parasitemia Microbiology Monocytes 03 medical and health sciences Mice 0302 clinical medicine Immune system Edema parasitic diseases medicine Translocator protein Leukocytes Macrophage Animals Lung Respiratory Distress Syndrome biology Macrophages Pneumonia biology.organism_classification medicine.disease Malaria Mice Inbred C57BL Disease Models Animal 030104 developmental biology Infectious Diseases medicine.anatomical_structure Positron-Emission Tomography biology.protein Parasitology medicine.symptom Fungal and Parasitic Infections Biomarkers |
| Zdroj: | Infect Immun |
| ISSN: | 1098-5522 |
| Popis: | Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a severe complication of malaria that occurs despite effective antimalarial treatment. Currently, noninvasive imaging procedures such as chest X-rays are used to assess edema in established MA-ARDS, but earlier detection methods are needed to reduce morbidity and mortality. The early stages of MA-ARDS are characterized by the infiltration of leukocytes, in particular monocytes/macrophages; thus, monitoring of immune infiltrates may provide a useful indicator of early pathology. In this study, Plasmodium berghei ANKA-infected C57BL/6 mice, a rodent model of MA-ARDS, were longitudinally imaged using the 18-kDa translocator protein (TSPO) imaging agent [(18)F]FEPPA as a marker of macrophage accumulation during the development of pathology and in response to combined artesunate and chloroquine diphosphate (ART+CQ) therapy. [(18)F]FEPPA uptake was compared to blood parasitemia levels and to levels of pulmonary immune cell infiltrates by using flow cytometry. Infected animals showed rapid increases in lung retention of [(18)F]FEPPA, correlating well with increases in blood parasitemia and pulmonary accumulation of interstitial inflammatory macrophages and major histocompatibility complex class II (MHC-II)-positive alveolar macrophages. Treatment with ART+CQ abrogated this increase in parasitemia and significantly reduced both lung uptake of [(18)F]FEPPA and levels of macrophage infiltrates. We conclude that retention of [(18)F]FEPPA in the lungs is well correlated with changes in blood parasitemia and levels of lung-associated macrophages during disease progression and in response to ART+CQ therapy. With further development, TSPO biomarkers may have the potential to accurately assess the early onset of MA-ARDS. |
| Databáze: | OpenAIRE |
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