Schistosomiasis-Induced Experimental Pulmonary Hypertension
| Autor: | Hazim El-Haddad, Rubin M. Tuder, Brian B. Graham, Angela Bandeira, Margaret M. Mentink-Kane, Elizabeth F. Redente, Hunter C. Champion, David W. H. Riches, Li Zhang, Paul M. Hassoun, Thomas A. Wynn, Ari L. Zaiman, Ghazwan Butrous, Shawn M. Purnell |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Lung biology medicine.medical_treatment Respiratory disease Interleukin biology.organism_classification medicine.disease Pulmonary hypertension Pathology and Forensic Medicine Cytokine Endocrinology medicine.anatomical_structure Internal medicine Interleukin 13 Immunology medicine Schistosoma mansoni Transforming growth factor |
| Zdroj: | The American Journal of Pathology. 177:1549-1561 |
| ISSN: | 0002-9440 |
| DOI: | 10.2353/ajpath.2010.100063 |
| Popis: | The mechanisms underlying schistosomiasis-induced pulmonary hypertension (PH), one of the most common causes of PH worldwide, remain unclear. We sought to determine whether Schistosoma mansoni causes experimental PH associated with pulmonary vascular remodeling in an interleukin (IL)-13-dependent manner. IL-13Rα1 is the canonical IL-13 signaling receptor, whereas IL-13Rα2 is a competitive nonsignaling decoy receptor. Wild-type, IL-13Rα1−/−, and IL-13Rα2−/− C57BL/6J mice were percutaneously infected with S. mansoni cercariae, followed by i.v. injection of eggs. We assessed PH with right ventricular catheterization, histological evaluation of pulmonary vascular remodeling, and detection of IL-13 and transforming growth factor-β signaling. Infected mice developed pulmonary peri-egg granulomas and arterial remodeling involving predominantly the vascular media. In addition, gain-of-function IL-13Rα2−/− mice had exacerbated vascular remodeling and PH. Mice with loss of IL-13Rα1 function did not develop PH and had reduced pulmonary vascular remodeling. Moreover, the expression of resistin-like molecule-α, a target of IL-13 signaling, was increased in infected wild-type and IL-13Rα2−/− but not IL-13Rα1−/− mice. Phosphorylated Smad2/3, a target of transforming growth factor-β signaling, was increased in both infected mice and humans with the disease. Our data indicate that experimental schistosomiasis causes PH and potentially relies on up-regulated IL-13 signaling. |
| Databáze: | OpenAIRE |
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