Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma.
BACKGROUND
Smooth muscle content is increased within the airway wall in patients with asthma and is likely to play a role in airway hyperresponsiveness. However, smooth muscle cells express several contractile and structural proteins, and each of these proteins may influence airway function distinctly.


OBJECTIVE
We examined the expression of contractile and structural proteins of smooth muscle cells, as well as extracellular matrix proteins, in bronchial biopsies of patients with asthma, and related these to lung function, airway hyperresponsiveness, and responses to deep inspiration.


METHODS
Thirteen patients with asthma (mild persistent, atopic, nonsmoking) participated in this cross-sectional study. FEV(1)% predicted, PC(20) methacholine, and resistance of the respiratory system by the forced oscillation technique during tidal breathing and deep breath were measured. Within 1 week, a bronchoscopy was performed to obtain 6 bronchial biopsies that were immunohistochemically stained for alpha-SM-actin, desmin, myosin light chain kinase (MLCK), myosin, calponin, vimentin, elastin, type III collagen, and fibronectin. The level of expression was determined by automated densitometry.


RESULTS
PC(20) methacholine was inversely related to the expression of alpha-smooth muscle actin (r = -0.62), desmin (r = -0.56), and elastin (r = -0.78). In addition, FEV(1)% predicted was positively related and deep inspiration-induced bronchodilation inversely related to desmin (r = -0.60), MLCK (r = -0.60), and calponin (r = -0.54) expression.


CONCLUSIONS
Airway hyperresponsiveness, FEV(1)% predicted, and airway responses to deep inspiration are associated with selective expression of airway smooth muscle proteins and components of the extracellular matrix.
Slats
Annelies M
AM
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. A.M.Slats@LUMC.nl
Janssen
Kirsten
K
van Schadewijk
Annemarie
A
van der Plas
Dirk T
DT
Schot
Robert
R
van den Aardweg
Joost G
JG
de Jongste
Johan C
JC
Hiemstra
Pieter S
PS
Mauad
Thais
T
Rabe
Klaus F
KF
Sterk
Peter J
PJ
D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001999:Bronchoscopy; D003430:Cross-Sectional Studies; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009124:Muscle Proteins / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000737:chemistry / Q000378:metabolism; D012129:Respiratory Function Tests
D016326:Extracellular Matrix Proteins; D009124:Muscle Proteins