Repeated allergen inhalation induces phenotypic modulation of smooth muscle in bronchioles of sensitized rats.
Repeated ovalbumin (OA) or saline exposure of sensitized Brown Norway rats was examined on agonist reactivity, airway smooth muscle (ASM) content, and contractile protein expression in small bronchioles at 24 h, 7 days, and 35 days after challenge. OA increased ASM content (P < 0.05 vs. saline) at 24 h, which resolved by 7 days. Maximum developed tension (T(max)) to carbachol, KCl, and 4-beta-phorbol 12,13-dibutyrate was increased (P < 0.05) by OA in bronchioles at 24 h but was abrogated after correction for ASM. Differences in T(max) were not present at 7 days. In contrast, at 35 days, T(max) was increased (P < 0.05) after correction for ASM. Smooth muscle (sm)-alpha-actin, sm-myosin heavy chain (MHC) isoform 1, calponin, smoothelin-A, and sm-myosin light chain kinase expression were reduced (P < 0.05) by OA at 24 h in bronchioles but not in trachealis. Consistent with contraction findings, no difference in expression of these proteins was detected at 7 days. At 35 days, however, with the exception of sm-alpha-actin, their abundance was again reduced (P < 0.05) by OA. Nonmuscle MHC and beta-actin were unchanged throughout by OA. These findings indicate persistent changes in contractile protein content, consistent with ASM phenotypic modulation in vivo, which occur in response to repeated OA inhalation. Thus, OA exposure induces structural changes in bronchiole ASM content and in agonist responsiveness ex vivo that resemble remodeling in asthma.
Moir
Lyn M
LM
Department of Asthma, Allergy and Respiratory Science, The Guy's, King's and St. Thomas' School of Medicine, King's College London, London SE1 9RT, UK.
Leung
Sum-Yee
SY
Eynott
Paul R
PR
McVicker
Clare G
CG
Ward
Jeremy P T
JP
Chung
K Fan
KF
Hirst
Stuart J
SJ
D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D001980:Bronchi / Q000502:physiology*; D016084:Bronchoconstriction / Q000276:immunology; D007114:Immunization; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000502:physiology*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D010641:Phenotype; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D000485:Allergens; D009124:Muscle Proteins; D010047:Ovalbumin