Mini-review: The role of mast cells in pulmonary hypertension

Abstract

Of recent, inflammatory responses, formation of ectopic lymphoid tissue and autoantibodies have been increasingly implicated in the pathophysiology of pulmonary hypertension (PH). One of the earliest immune cells detected in PH and implicated in its pathogenesis were mast cells based on their demonstrated abundance in the vicinity of vascular lesions in PH patients, as well as in lungs of animal models of PH. Experimental studies using mast cell stabilizers or mast cell deficient rats in classic PH models provided proof-of-principle for the functional relevance of mast cells in the initiation and/or progression of PH and lung vascular remodeling. Yet, the cellular mechanisms by which mast cells contribute to the development of PH and pulmonary vascular remodeling has so far remained largely unclear. Importantly, understanding the downstream effectors by which activated mast cells and their secretome trigger or promote vascular remodeling may lead to the development of novel therapies for PH. Notably, recent work has unveiled a novel interplay between mast cells and the adaptive immune system in PH, in that mast cell-targeted interventions attenuate the formation of tertiary lymphoid tissue in the lung and the formation of autoantibodies. This minireview will focus on the role of mast cells in PH and their possible downstream mechanism.