The Role of Hyaluronan in the Pulmonary Alveolus

Bray, Bonnie Anderson

doi:10.1006/jtbi.2001.2305

Cited by 37 publications

(36 citation statements)

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“…The molecular weight and concentration of HA for the in vivo study were selected on the basis of pilot studies. The molecular weight of HA used (250 kD) is close to the molecular weight (220 kD) of HA secreted by the alveolar cells (11,16) and has less apparent viscosity compared with higher molecular weight HA.…”

Section: Methodsmentioning

confidence: 84%

“…In normal alveolar fluid from rats, HA has an estimated concentration of~4 g/mL and a molecular weight of~220 kD (11). This may be an underestimation because of the inefficiency of removal of protein-bound HA and because of difficulties in ascertaining subphase volumes (17).…”

Section: Discussionmentioning

confidence: 99%

“…Forteza et al (8) proposed that HA plays a major role in mucosal host defense by stimulating ciliary beating via the RHAMM. Because HA is secreted into the alveolar subphase by type II cells (9,10), it has been suggested that it may interact with lung surfactant (11).…”

mentioning

confidence: 99%

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Hyaluronan Reduces Surfactant Inhibition and Improves Rat Lung Function after Meconium Injury

Goerke

Clements

et al. 2005

Pediatr Res

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Hyaluronan (HA), an ionic polymer, is normally present in the alveolar subphase and is known to decrease lung surfactant inactivation caused by serum in vitro. In this study, we examined whether HA can ameliorate the inactivating effects of meconium in vitro and in vivo. Surface activities of various mixtures of Survanta, HA, and meconium were measured using a modified pulsating bubble surfactometer. With meconium, almost all surface activity measures were improved by the addition of HA of several molecular weights at a concentration of 0.25%. Anesthetized, paralyzed rats were maintained on positive-pressure ventilation. After lung injury by instillation of meconium, they were treated with Survanta, Survanta with HA, or control mixtures. Serial measures of blood gases and peak inspiratory pressure were recorded for the duration of the experiment. When the Survanta plus HA group was compared with the Survanta alone group, arterial oxygen tension averaged 117% higher, peak inspiratory pressure was 27% lower at the end of the experiment, and lung compliance also showed significant improvement. These results indicate that HA added to Survanta decreases inactivation caused by meconium in vitro and improves gas exchange and pulmonary mechanics of animals with meconiuminduced acute lung injury. Abbreviations HA, hyaluronan (hyaluronic acid) PEG, polyethylene glycol PIP, peak inspiratory pressure PV, pressure-volume SA, surface area ⌬A 10 , percentage decrease in surface area from the maximum to reach a surface tension of 10 mN/m Hyaluronan (HA) is an ionic polymer of alternating Nacetylglucosamine and glucuronate units. It is one of the glycosaminoglycans that includes chondroitin, keratan, and heparan sulfates. Although HA has a simple chemical structure, it can assume a large number of conformations in aqueous solutions. These conformations allow HA to play many roles in biologic systems, such as being a space filler in the vitreous humor and serving as a viscoelastic substance in joints. In addition, HA interacts with cell surface receptors such as the receptor to HA-mediated motality RHAMM and CD44 (1-3). The biocompatibility of HA has led to many applications, including viscosurgery to allow the creation of space between tissues (4) and lubrication of arthritic joints.The role of HA in a variety of respiratory diseases has also been investigated by several groups. found that HA binds to elastic fibers, preventing elastolysis and limiting airspace enlargement in experimental models of emphysema induced by elastases. Forteza et al. (8) proposed that HA plays a major role in mucosal host defense by stimulating ciliary beating via the RHAMM. Because HA is secreted into the alveolar subphase by type II cells (9,10), it has been suggested that it may interact with lung surfactant (11).Our previous work has shown that adding HA to different lung surfactants improved the surface activity and decreased surfactant inactivation caused by serum (12). In this study, we investigated the effects of using HA Survanta mixtures i...

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Section: Methodsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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Hyaluronan Reduces Surfactant Inhibition and Improves Rat Lung Function after Meconium Injury

Goerke

Clements

et al. 2005

Pediatr Res

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“…The properties of HA include ability to self-aggregate, interactions with proteins, and ability to bind up to one thousand times its own weight of water (23,30). By binding water molecules, HA (like PEG and dextran) can increase the concentration of some molecules in the nonbound water and by this mechanism may act to segregate surfactant from serum constituents and thus mitigate inactivation.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan Decreases Surfactant Inactivation In Vitro

Goerke

Clements

et al. 2005

Pediatr Res

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Hyaluronan (HA) is an anionic polymer and a constituent of alveolar fluid that can bind proteins, phospholipids, and water. Previous studies have established that nonionic polymers improve the surface activity of pulmonary surfactants by decreasing inactivation of surfactant. In this work, we investigate whether HA can also have beneficial effects when added to surfactants. We used a modified pulsating bubble surfactometer to measure mixtures of several commercially available pulmonary surfactants or native calf surfactant with and without serum inactivation. Surface properties such as equilibrium surface tension, minimum and maximum surface tensions on compression and expansion of a surface film, and degree of surface area reduction required to reach a surface tension of 10 mN/m were measured. In the presence of serum, addition of HA dramatically improved the surface activities of all four surfactants and in some cases in the absence of serum as well. These results indicate that HA reduces inactivation of surfactants caused by serum and add evidence that endogenous HAs may interact with alveolar surfactant under normal and abnormal conditions. Over the past decade, pulmonary surfactant replacement has revolutionized the therapy of respiratory distress syndrome of premature infants (1-3). However, effects of surfactant therapy are less dramatic when used to treat lung diseases associated with acute lung injury and acute respiratory distress syndrome (4 -7). The less successful clinical response in these diseases may be due in part to surfactant inactivation caused by leakage of plasma and inflammatory products into the alveoli. In the presence of inactivating substances, surface activity of alveolar surfactant is adversely affected, worsening overall lung function (8,9).Variation in susceptibility to inactivation exists among therapeutic surfactants. Many studies have reported that surfactantassociated proteins help resist inactivation caused by a variety of factors (6). We and others have found that the addition of nonionic polymers [principally polyethylene glycol (PEG), or dextran] further reduces surfactant inactivation by serum, meconium, or other substances in vitro (10 -12). In vivo studies also demonstrate that the addition of nonionic polymers to therapeutic surfactants improves pulmonary function after lung injury caused by meconium, albumin, hydrochloric acid, milk acid, or endotoxin (11,(13)(14)(15)(16).The successful experiments with nonionic polymers led us to consider using ionic polymers. In this study, we investigated whether hyaluronan (HA) has effects on pulmonary surfactants that are similar to those described for dextran and PEG. HA is a nonsulfated, polymeric glycosaminoglycan (mucopolysaccharide) of N-acetyl-glucosamine linked ␤-1, 4 to glucuronic acid, which is linked ␤-1, 3 to N-acetylglucosamine, etc. Unlike PEG or dextran, HA, an anionic polymer, is a natural, ubiquitous substance in the body. However, HA (like PEG and dextran) shares the ability to bind water but has much greater bind...

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“…Corneal shields based on Hyaluronic acid have demonstrated prolonged steroid delivery, with a consummate smoothing of dosage profile [87]. Other applications of hyaluronic acid as reviewed by Price et al, [88] are as follows: (i) Wound healing by extracellular regeneration; (ii) Epithelial regeneration; (iii) Topical treatment of dry eye syndrome [89] and Sjögren's syndrome [90]; (iv) as a viscosity agent in pulmonary pathology for achieving alveolar patency [91]; (v) Commercial preparation available for intraarticular injection; (vi) As a filler in rejuvenative medicine for wrinkles and cutaneous lines. Viscosupplementation with Hyaluronic acid products helps to improve the physiological environment in an osteoarthritic joint by supplementing the shock absorption and lubrication properties of osteoarthritic synovial fluid.…”

Section: Hyaluronic Acidmentioning

confidence: 99%