title: Ultrastructure of human tracheal smooth muscle from subjects with asthma and nonasthmatic subjects. Standardized methods for comparison.
abstract: A characteristic feature of asthma is exaggerated airway narrowing, termed airway hyper-responsiveness (AHR) due to contraction of airway smooth muscle (ASM). Although smooth muscle (SM)-specific asthma susceptibility genes have been identified, it is not known whether asthmatic ASM is phenotypically different from nonasthmatic ASM in terms of subcellular structure or mechanical function. The present study is the first to systematically quantify, using electron microscopy, the ultrastructure of tracheal SM from subjects with asthma and nonasthmatic subjects. Methodological details concerning tissue sample preparation, ultrastructural quantification, and normalization of isometric force by appropriate morphometric parameters are described. We reasoned that genetic and/or acquired differences in the ultrastructure of asthmatic ASM could be associated with functional changes. We recently reported that asthmatic ASM is better able to maintain and recover active force generation after length oscillations simulating deep inspirations. The present study was designed to seek structural evidence to account for this observation. Contrary to our hypotheses, no significant qualitative or quantitative differences were found in the subcellular structure of asthmatic versus nonasthmatic tracheal SM. Specifically, there were no differences in average SM cell cross-sectional area; fraction of the cell area occupied by nonfilamentous area; amounts of mitochondria, dense bodies, and dense plaques; myosin and actin filament densities; basal lamina thickness; and the number of microtubules. These results indicate that functional differences in ASM do not necessarily translate into observable structural changes.
authors: Departments of 1 Pathology and Laboratory Medicine.
authors: Harley T
authors: HT
authors: Syyong
authors: Chris D
authors: CD
authors: Pascoe
authors: Jenny
authors: J
authors: Zhang
authors: Bryna A
authors: BA
authors: Arsenault
authors: Dennis
authors: D
authors: Solomon
authors: W Mark
authors: WM
authors: Elliott
authors: Tillie L
authors: TL
authors: Hackett
authors: David C
authors: DC
authors: Walker
authors: Peter D
authors: PD
authors: Paré
authors: Chun Y
authors: CY
authors: Seow
mesh_terms: D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism / Q000648:ultrastructure*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure; D009218:Myosins / Q000378:metabolism / Q000648:ultrastructure; D014132:Trachea / Q000378:metabolism / Q000648:ultrastructure*; D055815:Young Adult
chemical_list: D000199:Actins; D009218:Myosins
keywords: electron microscopy; force normalization; quantitative morphometry