Experimental models for studying mucociliary clearance

Abstract

Respiratory tract mucus is a viscoelastic gel, the rheological properties of which are determined mainly by its content of mucous glycoproteins and water. The rheology and quantity of mucus, in concert with ciliary factors, are the major determinants of mucociliary clearance.A wide range of animal models for studying the secretion and clearance of mucus are available. Ex vivo models, such as the frog palate or excised bovine trachea, provide direct, meaningful data regarding the clearability of mucus. Rodent models of chronic bronchitis, based on irritant gas or cigarette smoke exposure, show important features of the human condition in a relatively short time. The rheological characterization of mucus is made difficult by the small quantities obtainable, particularly from normal animals.Large animal models, such as the dog or sheep, although more expensive, offer many advantages, such as the ability to carry out long-term serial measurements, and to make integrated measurements of the clearance of mucus, ciliary function, epithelial ion transport, and the rheology of mucus in the same preparation. Eur Respir J 1998; 11: 222-228 The viscoelastic properties of mucusDue to the cross-linking of glycoproteins, the rheological behaviour of mucus is described as viscoelastic, having characteristics of both a liquid and a solid [1,2]. Viscosity is the resistance to flow, and represents the capacity of a material to absorb energy as it moves. Elasticity is the capacity of a material to store the energy used to move or deform it. With ideal fluids, viscosity is independent of the stress applied. With viscoelastic liquids, such as mucus, viscosity decreases with increasing stress or rate of strain (shear rate). Mucus responds to stress with an initial solid-like deformation, followed by a viscoelastic deformation and finally by a period of steady flow, in which the rate of deformation is constant. Only partial recovery of the strain follows removal of the stress, indicating a permanent deformation of its gel structure. Changes in the viscosity and elasticity of mucus are generally interrelated.Mucus exhibits shear-thinning following exposure to high shear forces, exhibiting a decreased viscosity at low shear rates. Some shear-thinning may be permanent, indicating altered molecular structure, whilst some shearthinning, termed "thixotropy", may be reversible.The viscoelasticity of mucus can be effectively described by two relatively independent quantities, G* and tangent (tan) δ, which vary with measurement frequency. The mechanical impedance (G*), is the vector sum of viscosity and elasticity; it can be termed the "rigidity factor". Tan δ is the ratio of viscosity to elasticity; it is also known as the loss tangent and can be considered as a "recoil factor". The relative proportions of elasticity and viscosity are important in describing how a material, such as mucus, behaves when it is subjected to external forces. Rheological assessment of mucus Collection of mucusTracheal mucus can be collected by a modificat...

Cyclosporin a Reduces Airway Mucus Secretion and Mucociliary Clearance in Rats

“…33 Due to the cross-linking of glycoproteins, the rheological behavior of mucus is described as viscoelastic, having characteristics of both a liquid and a solid. 34 The relative proportions of elasticity and viscosity are important in describing how a material such as mucus behaves when it is subjected to external forces. The ratio of viscosity to elasticity is also an important determinant of mucociliary clearance.…”

“…In addition, the ionic channels probably regulate the hydration degree of the gel phase, thus modulating its rheological properties. 34 To assess whether CsA also affects the amount of mucus secretion from goblet cells, we quantified both acid and neutral mucus in respiratory epithelium. Airway mucins are thought to be derived from periodic-acid-Schiff (PAS)-positive secretory granules ("mucous" granules) found in 2 different cell types in the airway: goblet cells of the surface epithelium and mucous cells of the submucosal glands.…”

“…Mucus samples were collected by placing a soft-bristled brush against the pulmonary airway and removing the brush once it was covered with sufficient mucus for analysis. 20 The in vitro transport rate was evaluated by using a bullfrog (Rana catesbeiana) palate model. Briefly, the transport velocity of the mucus sample placed on a frog palate was determined with the aid of a stereomicroscope fitted with a micrometer scale.…”

Avaliação da resposta inflamatória pulmonar e do transporte mucociliar em modelo de inflamação alérgica pulmonar: modulação pelo estresse induzido pela natação forçada

“…Esta camada de muco do epitélio respiratório serve para conduzir as partículas nocivas que são inaladas, e devem possuir características reológicas adequadas para melhor aproveitamento da energia cinética fornecida pelo batimento ciliar. Além disso, possui também importante atividade antimicrobiana e neutralizadora de agentes químicos nocivos (Saldiva, 1990 (King, 1998).…”

“…Para o estudo do transporte mucociliar optamos por desenvolver um modelo ex vivo, utilizando a própria traquéia do animal. Este modelo foi adaptado de outros previamente utilizados neste laboratório, tais como: modelo de avaliação in situ, utilizada para estudo do efeito da reanastomose brônquica no transporte mucociliar de ratos (Rivero et al, 2001), modelo de avaliação ex vivo no palato de rã, amplamente utilizado para avaliar o transporte mucociliar (Saldiva, 1990;King, 1998;Carvalho-Oliveira et al, 2005;Teixeira et al, 2006). O desenvolvimento deste modelo permitiu avaliar a interação Alguns estudos experimentais mostraram que a terapia com corticosteróides pode suprimir a produção de muco, inibindo diretamente as células caliciformes assim como reduzindo as citocinas pró-inflamatórias que estimulam a produção de muco (Kai et al, 1996;Lu et al, 2005).…”