Chemokine signaling axis between endothelial and myeloid cells regulates development of pulmonary hypertension associated with pulmonary fibrosis and hypoxia.
Am J Physiol Lung Cell Mol Physiol
; 317(4): L434-L444, 2019 10 01.
Article
en En
| MEDLINE
| ID: mdl-31364370
ABSTRACT
Pulmonary hypertension complicates the care of many patients with chronic lung diseases (defined as Group 3 pulmonary hypertension), yet the mechanisms that mediate the development of pulmonary vascular disease are not clearly defined. Despite being the most prevalent form of pulmonary hypertension, to date there is no approved treatment for patients with disease. Myeloid-derived suppressor cells (MDSCs) and endothelial cells in the lung express the chemokine receptor CXCR2, implicated in the evolution of both neoplastic and pulmonary vascular remodeling. However, precise cellular contribution to lung disease is unknown. Therefore, we used mice with tissue-specific deletion of CXCR2 to investigate the role of this receptor in Group 3 pulmonary hypertension. Deletion of CXCR2 in myeloid cells attenuated the recruitment of polymorphonuclear MDSCs to the lungs, inhibited vascular remodeling, and protected against pulmonary hypertension. Conversely, loss of CXCR2 in endothelial cells resulted in worsened vascular remodeling, associated with increased MDSC migratory capacity attributable to increased ligand availability, consistent with analyzed patient sample data. Taken together, these data suggest that CXCR2 regulates MDSC activation, informing potential therapeutic application of MDSC-targeted treatments.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fibrosis Pulmonar
/
Transducción de Señal
/
Receptores de Interleucina-8B
/
Células Endoteliales
/
Células Supresoras de Origen Mieloide
/
Hipertensión Pulmonar
/
Hipoxia
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Am J Physiol Lung Cell Mol Physiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Año:
2019
Tipo del documento:
Article