Extrinsic and intrinsic airway obstruction is related to different airway smooth muscle phenotypes

Abstract

Airway obstruction (AO) in asthma is driven by airway smooth muscle (ASM) contraction. Direct stimulation of ASM with contractile agonists, or indirect with antigens are related to extrinsic induced AO; while airway baseline tone (ABT) depend on intrinsic AO. The ASM phenotype involved in these types of AO seems to be related. To associate the ASM phenotype involved in each type of AO, guinea pigs were sensitized and challenged with ovalbumin. At third challenge, airway responsiveness (AR) to histamine and lung samples were obtained. ASM cells (ASMc) were isolated to determinate by flow cytometry, the number of cells that express transforming growth factor-β1 (TGF-β1), interleukin-13 (IL-13) and sarco-endoplasmic Ca2+ATPase-2b (SERCA2b). Control guinea pigs received saline instead antigen. Allergen challenges induced AO and increment in ABT. The AR and TGF-β1 in ASMc increased asthma. No change was observed in airway wall area and IL-13 and SERCA2b in ASMc. SERCA2B gene expression and reduced glutathione (GSH) levels were abated in asthma. The extent of antigen-induced AO was associated with ASMc TGF-β1 levels and AR degree. The magnitude of AR and antigen-induced AO had an inverse relation with GSH levels. ABT extent showed an inverse association with SERCA2b. No relation was observed between direct or indirect AO with ABT. In conclusion, each type of AO is associated with different ASM phenotype: 1) direct and indirect AO seems to be sensitive to the level of ASM oxidative stress, 2) indirect AO induced by antigen appears to be influenced by ASMc TGF-β1 and, 3) SERCA2b expression level in ASMc has a role in ABT. SEP-CONACyT (# 256197)