Ana M. Herrera

Ultrastructure of airway smooth muscle.

There is an abundance of ultrastructural data in the literature on vascular, visceral, and other smooth muscles; such data on airway smooth muscle, however, are conspicuously missing. Here we present a series of electron micrographs depicting contractile and cytoskeletal elements as well as organelles in porcine trachealis. Myosin thick filaments are present in the relaxed muscle; thick filament density increases substantially when the muscle is activated. Actin thin filaments are present in large excess over the thick filaments; the thin/thick filament ratio is about 31/1 in the relaxed state; this ratio is reduced to about 22/1 when the muscle is activated. The sarcoplasmic reticulum is often found associated with caveolae and mitochondria. Cells within a bundle are well connected by intermediate and gap junctions. The results demonstrate that quantitative morphological analysis of ultrastructure of airway smooth muscle fixed under different functional states is possible and will be essential in elucidating the structural basis of adaptation and contraction of the muscle.

Fibrotic Response of Tissue Remodeling in COPD

Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) involves diverse processes characterized by epithelial disruption, smooth muscle hypertrophy/hyperplasia, airway wall fibrosis, and alveolar destruction. According to the accepted current theory of COPD pathogenesis, tissue remodeling in COPD is predominantly a consequence of an imbalance between proteolytic and antiproteolytic activities. However, most of the studies carried out during the last few years have focused on mechanisms related to degradation of extracellular matrix (ECM) structural proteins, neglecting those involved in ECM protein deposition. This review revisits some of the latest findings related to fibrotic changes that occur in the airway wall of COPD patients, as well as the main cellular phenotypes relevant to these processes.

Dense-body aggregates as plastic structures supporting tension in smooth muscle cells

The wall of hollow organs of vertebrates is a unique structure able to generate active tension and maintain a nearly constant passive stiffness over a large volume range. These properties are predominantly attributable to the smooth muscle cells that line the organ wall. Although smooth muscle is known to possess plasticity (i.e., the ability to adapt to large changes in cell length through structural remodeling of contractile apparatus and cytoskeleton), the detailed structural basis for the plasticity is largely unknown. Dense bodies, one of the most prominent structures in smooth muscle cells, have been regarded as the anchoring sites for actin filaments, similar to the Z-disks in striated muscle. Here, we show that the dense bodies and intermediate filaments formed cable-like structures inside airway smooth muscle cells and were able to adjust the cable length according to cell length and tension. Stretching the muscle cell bundle in the relaxed state caused the cables to straighten, indicating that these intracellular structures were connected to the extracellular matrix and could support passive tension. These plastic structures may be responsible for the ability of smooth muscle to maintain a nearly constant tensile stiffness over a large length range. The finding suggests that the structural plasticity of hollow organs may originate from the dense-body cables within the smooth muscle cells.

Myosin filaments in smooth muscle cells do not have a constant length.

•  The length of myosin filaments was measured in three types of smooth muscle using serial electron microscopy. •  The frequency distribution of myosin filament length for all three types of smooth muscle followed an exponential decay pattern. •  The same frequency distribution pattern was observed in activated tracheal smooth muscle, although the average length was shorter compared with the filaments in relaxed smooth muscle. •  Analysis suggests that the distribution pattern reflects a dynamic equilibrium between competing processes of linear polymerization and de‐polymerization of myosin dimers.

Vitronectin Expression in the Airways of Subjects with Asthma and Chronic Obstructive Pulmonary Disease

Vitronectin, a multifunctional glycoprotein, is involved in coagulation, inhibition of the formation of the membrane attack complex (MAC), cell adhesion and migration, wound healing, and tissue remodeling. The primary cellular source of vitronectin is hepatocytes; it is not known whether resident cells of airways produce vitronectin, even though the glycoprotein has been found in exhaled breath condensate and bronchoalveolar lavage from healthy subjects and patients with interstitial lung disease. It is also not known whether vitronectin expression is altered in subjects with asthma and COPD. In this study, bronchial tissue from 7 asthmatic, 10 COPD and 14 control subjects was obtained at autopsy and analyzed by immunohistochemistry to determine the percent area of submucosal glands occupied by vitronectin. In a separate set of experiments, quantitative colocalization analysis was performed on tracheobronchial tissue sections obtained from donor lungs (6 asthmatics, 4 COPD and 7 controls). Vitronectin RNA and protein expressions in bronchial surface epithelium were examined in 12 subjects who undertook diagnostic bronchoscopy. Vitronectin was found in the tracheobronchial epithelium from asthmatic, COPD, and control subjects, although its expression was significantly lower in the asthmatic group. Colocalization analysis of 3D confocal images indicates that vitronectin is expressed in the glandular serous epithelial cells and in respiratory surface epithelial cells other than goblet cells. Expression of the 65-kDa vitronectin isoform was lower in bronchial surface epithelium from the diseased subjects. The cause for the decreased vitronectin expression in asthma is not clear, however, the reduced concentration of vitronectin in the epithelial/submucosal layer of airways may be linked to airway remodeling.