Playing a dirty trick on airway smooth muscle: house dust mite does it again.

摘要

Increased airway smooth muscle (ASM) mass is a hallmark of asthma and is thought to be the main contributor to the increased airway hyperresponsiveness seen in asthmatics [1]. This increase is related to disease severity (reviewed in [2]) and caused by hyperplasia alone or in combination with hypertrophy, depending on the generation of airways [3, 4]. Why and how ASM mass is increased is incompletely understood, but in vitro studies have shown that ASM cells isolated from asthmatics proliferate faster in culture [5]. In addition, cultured patient cells produce more chemokines and an altered array of extracellular matrix proteins compared with those of healthy individuals [6, 7]. In vitro studies have shown that upon isolation, ASM cells display contractile function, but they rapidly change phenotype {i.e. acquire proliferative and synthetic capacity) and become noncontractile during culture under serum-rich conditions [8]. When these synthetic-pro-liferative cells are serum-deprived for a prolonged period of time, a small population (so-called "hypercontractile" cells) starts re-expressing contractile protein genes, such as ACTA2 (encoding alpha-smooth muscle actin (alpha-SMA)) [9]. This dediffer-entiation/modulation and differentiation/maturation of ASM cells is referred to as phenotype switching or phenotypic plasticity, and although this phenomenon clearly exists in vitro, we do not know whether this plays a role in thickening of the ASM layer.