Role of airway smooth muscle cell phenotypes in airway tone and obstruction in guinea pig asthma model
Por:
Alvarez-Santos, Mayra D., Alvarez-Gonzalez, Marisol, Eslava-De-Jesus, Elizabeth, Gonzalez-Lopez, Angel, Pacheco-Alba, Ivonne, Perez-Del-Valle, Yazmin, Rojas-Madrid, Rodrigo, Bazan-Perkins, Blanca
Publicada:
11 ene 2022
Resumen:
Background: Airway obstruction (AO) in asthma is driven by airway smooth
muscle (ASM) contraction. AO can be induced extrinsically by direct
stimulation of ASM with contractile agonists as histamine, or by
indirect provocation with antigens as ovalbumin, while the airway tone
is dependent on intrinsic mechanisms. The association of the ASM
phenotypes involved in different types of AO and airway tone in guinea
pigs was evaluated.
Methods: Guinea pigs were sensitized to ovalbumin and challenged with
antigen. In each challenge, the maximum OA response to ovalbumin was
determined, and before the challenges, the tone of the airways. At third
challenge, airway responsiveness (AR) to histamine was evaluated and ASM
cells from trachea were disaggregated to determinate: (a) by flow
cytometry, the percentage of cells that express transforming growth
factor-beta 1 (TGF-beta 1), interleukin-13 (IL-13) and sarco-endoplasmic
Ca2+ ATPase-2b (SERCA2b), (b) by RT-PCR, the SERCA2B gene expression,
(c) by ELISA, reduced glutathione (GSH) and, (d) Ca2+ sarcoplasmic
reticulum refilling rate by microfluorometry. Control guinea pig group
received saline instead ovalbumin.
Results: Antigenic challenges in sensitized guinea pigs induced indirect
AO, AR to histamine and increment in airway tone at third challenge. No
relationship was observed between AO induced by antigen and AR to
histamine with changes in airway tone. The extent of antigen-induced AO
was associated with both, TGF-beta 1 expression in ASM and AR degree.
The magnitude of AR and antigen-induced AO showed an inverse correlation
with GSH levels in ASM. The airway tone showed an inverse association
with SERCA2b expression.
Conclusions: Our data suggest that each type of AO and airway tone
depends on different ASM phenotypes: direct and indirect AO seems to be
sensitive to the level of oxidative stress; indirect obstruction induced
by antigen appears to be influenced by the expression ofTGF-beta 1 and
the SERCA2b expression level plays a role in the airway tone.
Filiaciones:
Alvarez-Santos, Mayra D.:
Univ Nacl Autonoma Mexico, Fac Ciencias, Biol Area, Mexico City 04510, DF, Mexico
Alvarez-Gonzalez, Marisol:
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Inmunofarmacol, Mexico City 14080, DF, Mexico
Eslava-De-Jesus, Elizabeth:
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Inmunofarmacol, Mexico City 14080, DF, Mexico
Gonzalez-Lopez, Angel:
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Inmunofarmacol, Mexico City 14080, DF, Mexico
Pacheco-Alba, Ivonne:
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Inmunofarmacol, Mexico City 14080, DF, Mexico
Perez-Del-Valle, Yazmin:
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Inmunofarmacol, Mexico City 14080, DF, Mexico
Rojas-Madrid, Rodrigo:
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Inmunofarmacol, Mexico City 14080, DF, Mexico
Bazan-Perkins, Blanca:
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Inmunofarmacol, Mexico City 14080, DF, Mexico
Tecnol Monterrey, Escuela Med & Ciencias Salud, Mexico City 14380, DF, Mexico
Green Published, gold, Gold, Green
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