Journal article

Publication year: 2012

Pages: 897-908

Journal: American Journal of Respiratory and Critical Care Medicine

Volume number: 186

Issue number: 9

ISSN: 1073-449X

eISSN: 1535-4970

DOI Link: https://doi.org/10.1164/rccm.201202-0335OC

Publisher: American Thoracic Society

Abstract: 

Rationale: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling. Recent studies have revealed that immune and inflammatory responses play a crucial role in pathogenesis of idiopathic PAH.

Objectives: To systematically evaluate the number and cross-sectional distribution of inflammatory cells in different sizes of pulmonary arteries from explanted lungs of patients with idiopathic PAH versus healthy donor lungs and to demonstrate functional relevance by blocking stromal-derived factor-1 by the Spiegelmer NOX-A12 in monocrotaline-induced pulmonary hypertension in rats.

Methods: Immunohistochemistry was performed on lung tissue sections from patients with idiopathic PAH and healthy donors. All positively stained cells in whole-lung tissue sections, surrounding the vessels, and in the different compartments of the vessels were counted. To study the effects of blocking SDF-1, rats with monocrotaline-induced pulmonary hypertension were treated with NOX-A12 from Day 21 to Day 35 after monocrotaline administration.

Measurements and Main Results: We found a significant increase of the perivascular number of macrophages (CD68(+)), macrophages/monocytes (CD14(+)), mast cells (toluidine blue), dendritic cells (CD209(+)), T cells (CD3(+)), cytotoxic T cells (CD8(+)), and helper T cells (CD4(+)) in vessels of idiopathic PAH lungs compared with control subjects. FoxP3(+) mononuclear cells were significantly decreased. In the monocrotaline model, the NOX-A12-induced reduction of mast cells, CD68(+) macrophages, and CD3(+) T cells was associated with improvement of hemodynamics and pulmonary vascular remodeling.

Conclusions: Our findings reveal altered perivascular inflammatory cell infiltration in pulmonary vascular lesions of patients with idiopathic pulmonary arterial hypertension. Targeting attraction of inflammatory cells by blocking stromal-derived factor-1 may be a novel approach for treatment of PAH.

Harvard Citation style: Savai, R., Pullamsetti, S., Kolbe, J., Bieniek, E., Voswinckel, R., Fink, L., et al. (2012) Immune and Inflammatory Cell Involvement in the Pathology of Idiopathic Pulmonary Arterial Hypertension, American Journal of Respiratory and Critical Care Medicine, 186(9), pp. 897-908. https://doi.org/10.1164/rccm.201202-0335OC

APA Citation style: Savai, R., Pullamsetti, S., Kolbe, J., Bieniek, E., Voswinckel, R., Fink, L., Scheed, A., Ritter, C., Dahal, B., Vater, A., Klussmann, S., Ghofrani, H., Weissmann, N., Klepetko, W., Banat, G., Seeger, W., Grimminger, F., & Schermuly, R. (2012). Immune and Inflammatory Cell Involvement in the Pathology of Idiopathic Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine. 186(9), 897-908. https://doi.org/10.1164/rccm.201202-0335OC