Hyaluronan Decreases Surfactant Inactivation In Vitro

Abstract

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...

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

“…chitosan and HA). For instance, addition of 2.5 mg/mL HA to 0.5 mg/mL BLES impairs adsorption; however, previous studies showed that 2.5 mg/mL HA improved the surface activity of 1.25 mg/mL therapeutic surfactants (10,11), i.e. at a concentration higher than the BLES concentration in the present study.…”

“…More recently, Lu et al (10,11) reported the use of an anionic polymer, HA, as a surfactant additive. Both in vitro (10) and in vivo (11) tests showed that the addition of HA at different molecular weights to various therapeutic lung surfactants can effectively reverse serum-and meconium-induced inactivation.…”

“…Both in vitro (10) and in vivo (11) tests showed that the addition of HA at different molecular weights to various therapeutic lung surfactants can effectively reverse serum-and meconium-induced inactivation. These studies, therefore, tentatively proved the feasibility of using an ionic polymer as a lung surfactant additive.…”

“…To further characterize the performance of chitosan, the effects of PEG (10 kD), which is the most effective nonionic polymer tested so far (1,5), and, HA (1240 kD), i.e. the most effective HA molecular weight (10,11), are also studied under the same conditions and compared with the effects of chitosan.…”

Polyethylene Glycol-Surfactant for Lavage Lung Injury in Rats

“…Multiple reports indicate improved surfactant function when polymers such as dextrans, PEG, and hyaluronan are added to surfactant preparations in vitro (12)(13)(14)(15). Animals with ALI have improved lung function when treated with surfactant polymer mixtures versus surfactant alone.…”