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Original Research |

Circulating Myeloid-Derived Suppressor Cells Are Increased and Activated in Pulmonary HypertensionMyeloid Suppressor Cells in Pulmonary Hypertension

Michael E. Yeager, PhD; Cecilia M. Nguyen, BS; Dmitry D. Belchenko, BA; Kelley L. Colvin, MS; Shinichi Takatsuki, MD; D. Dunbar Ivy, MD, FCCP; Kurt R. Stenmark, MD
Author and Funding Information

From the Department of Pediatrics, Division of Pulmonary and Critical Care Medicine (Drs Yeager and Stenmark, Ms Nguyen, and Mr Belchenko), the Department of Pediatrics, Pulmonary Hypertension Program and Pediatric Heart Lung Center, Children’s Hospital (Dr Ivy and Ms Colvin), and the Gates Center for Regenerative Medicine and Stem Cell Biology (Dr Stenmark), University of Colorado, Denver, Aurora, Colorado; and the Department of Pediatrics, Omori Medical Center (Dr Takatsuki), Toho University, Tokyo, Japan.

Correspondence to: Michael E. Yeager, PhD, University of Colorado Denver Health Sciences, Pediatrics Critical Care, 12700 E 19th Ave, Box C218, Aurora, CO 80045; e-mail: michael.yeager@ucdenver.edu


Funding/Support: This study was funded by an Actelion Entelligence Young Investigator Award to Dr Yeager; the National Institutes of Health, Specialized Centers of Clinically Oriented Research [Grant HL-084923-020]; the National Institutes of Health, Program Project [Grant HL-014985-35]; the Jayden DeLuca Foundation; the National Institutes of Health, General Clinical Research Center National Center for Research Resources [Grant M01-RR00069]; and the Leah Bult Pulmonary Hypertension Research Fund.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(4):944-952. doi:10.1378/chest.11-0205
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Background:  Myeloid-derived suppressor cells (MDSCs) are increased in inflammatory and autoimmune disorders and orchestrate immune cell responses therein. Pulmonary hypertension (PH) is associated with inflammation, autoimmunity, and lung vascular remodeling. Immature myeloid cells are found in the lungs of humans and animals with PH, and we hypothesized that they would be increased in the blood of patients with PH compared with control subjects.

Methods:  Twenty-six children with PH and 10 undergoing cardiac catheterization for arrhythmia ablation were studied. Five milliliters of fresh blood were analyzed using flow cytometry. Results were confirmed using magnetic bead sorting and immunofluorescence, while quantitative polymerase chain reaction and intracellular urea concentration assays were used as measures of MDSC arginase-1 activation.

Results:  Flow cytometry demonstrated enrichment of circulating MDSCs among patients with PH (n = 26; mean, 0.271 × 106 cells/mL ± 0.17; 1.86% of CD45+ population ± 1.51) compared with control subjects (n = 10; mean, 0.176 × 106 cells/mL ± 0.05; 0.57% of CD45+ population ± 0.29; P < .05). Higher numbers of circulating MDSCs correlated to increasing mean pulmonary artery pressure (r = 0.510, P < .05). Among patients with PH, female patients had a twofold increase in MDSCs compared with male patients. Immunofluorescence analysis confirmed the results of flow cytometry. Quantitative reverse transcription polymerase chain reaction assay results for arginase-1 and measurement of intracellular urea concentration revealed increased activity of MDSCs from patients with PH compared with control subjects.

Conclusions:  Circulating activated MDSCs are significantly increased in children with PH compared with control subjects. Further investigation of these cells is warranted, and we speculate that they might play significant immunomodulatory roles in the disease pathogenesis of PH.

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