Natural Killer Cells in Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disorder of the pulmonary vasculature characterized by the constriction of precapillary pulmonary arteries, leading to sustained elevated pressure in pulmonary vessels. The chronic strain and then failure of the right heart leads to significant morbidity and mortality in affected patients. In untreated patients the prognosis can be as poor as in patients with malignancies. Article see p 1099 The pathophysiology of PAH is unclear. Histological features reveal proliferation of endothelial and smooth muscle cells with vascular remodeling resulting from the formation of plaquelike lesions with fibroblasts, smooth muscle cells, and endothelial cells. Dysregulated angiogenesis, morphological and functional alterations of microvessels are hallmark features of chronic inflammatory disorders. It is generally accepted that peripheral and coronary vascular disease is linked strongly to inflammatory processes.1 There is growing evidence for a fundamental involvement of inflammatory processes in PAH. For decades it has been recognized that immune phenomena are associated with PAH.2 Inflammatory cells and intense chemokine production have been detected within remodeled pulmonary arteries, but it has not been clear whether the complex phenomenon we call inflammation surrounding the pulmonary vasculature is primarily the cause or the consequence of vascular remodeling. Perivascular T and B lymphocytes have been detected in pulmonary vascular PAH lesions.3 A recent study further shows that pathogenic antibodies and corresponding T cells may also be generated locally in the lung, in highly organized ectopic lymphoid follicles, with stimulating autoantibodies as possible mediators of PAH,4 which suggests that the adaptive immune system is involved. Although a role of the adaptive immune system, especially of T lymphocytes, in the initiation and progression of PAH was demonstrated, the contribution of effectors of the innate immune system has only recently come into focus. In the current issue of Circulation , Ormiston …