Changes in Hyaluronan Deposition during Early Respiratory Distress Syndrome in Premature Monkeys

Juul, Sandra E.; Kinsella, Michael G.; Jackson, J. Craig; Truog, William E.; Standaert, T. A.; Hodson, W. Alan

doi:10.1203/00006450-199402000-00024

Cited by 37 publications

(22 citation statements)

References 18 publications

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“…Various lung injuries result in either increased or decreased levels of HA (34,35). Inflammatory processes have been found to be affected in vivo by HA in part dependent on molecular weight (36 -38).…”

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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Section: Discussionmentioning

confidence: 99%

Hyaluronan Decreases Surfactant Inactivation In Vitro

Goerke

Clements

et al. 2005

Pediatr Res

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“…In this context, it is worthy to note that an increased lung HA concentration and water content have been demonstrated in neonatal respiratory distress syndrome (35,36) and in preterm and term rabbit pups during exposure to oxygen breathing (37).…”

Section: Lung Water and Hyaluronan In Rabbit Pupsmentioning

confidence: 99%

Lung Water and Proton Magnetic Resonance Relaxation in Preterm and Term Rabbit Pups: Their Relation to Tissue Hyaluronan

et al. 2000

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The present study was performed to investigate simultaneously total lung water, T 1 and T 2 relaxation times, and hyaluronan (HA) in preterm and term rabbits. Attempts were also made to establish the relationship of HA to total lung water and to T 2 -derived motionally distinct water fractions. Experiments were performed in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29, and 31 d and at a postnatal age of 4 d. Lung tissue water content (desiccation method), T 1 and T 2 relaxation times (H 1 -NMR method), and HA concentration (radioassay) were measured, and free and bound water fractions were calculated by using multicomponent fits of the T 2 relaxation curves. Lung water content and T 1 and T 2 relaxation times were highest at a gestational age of 27 d and then declined steadily during the whole study period. Similar trends and time courses were seen for the fast and slow components of the T 2 relaxation curve. The T 2 -derived free water fraction remained unchanged at a gestational age of 25-29 d (ϳ67%), but increased progressively to a value of 78.5 Ϯ 7. During fetal life the potential air space of the lung is filled with fluid, which is generated by continuous epithelial secretion driven by active chloride transport. As parturition approaches, the lung fluid secretion decreases, and sodium transport-dependent reabsorption begins. This switch in transepithelial water movement culminates at birth and results in rapid clearance of lung fluid, which is critical for successful transition to air breathing (1-4).The osmotic water permeability of the alveolar epithelium is developmentally regulated by and related to the expression of water-transporting proteins, called AQPs. Three AQPs have been identified in the lung: AQP1 in the capillary endothelium, AQP4 in the basolateral membrane of the airway epithelium, and AQP5 in the apical membrane of alveolar epithelial type I cells (5-8).The specific localization of AQPs to endothelial and epithelial cells suggests water movement between the air space and the interstitial and capillary compartments. It takes place through individual water channels. The mRNA and protein expression of AQPs appears late in gestation, increases markedly at birth, and remains elevated during early postnatal life (9, 10). This developmental pattern of AQP expression parallels perinatal changes in the osmotic water permeability of the lung and the rate of lung water removal that occurs around birth (11).In addition to active ion transport-driven AQP-mediated water transport, the physical state of tissue water is also an important determinant of perinatal lung water clearance. Namely, a fraction of tissue water is motionally constrained, i.e. bound to macromolecules and thus made unavailable for immediate transport across alveolar, microvascular, and airway barriers (12).

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“…It appears in abundance in tissues during fetal development or repair, and during inflammatory processes (17). The lung hyaluronan concentration in rabbit fetuses normally decreases progressively toward term (18), but may increase in association with neonatal pulmonary diseases, including respiratory distress syndrome (19), and after hyperoxia (20).…”

mentioning

confidence: 99%

Antenatal Betamethasone Administration Decreases the Lung Hyaluronan Concentration in Preterm Rabbit Pups

2001

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Maternal treatment with corticosteroids before preterm delivery is effective in reducing the incidence of respiratory distress syndrome and neonatal mortality. We hypothesized that corticosteroids might lower the lung hyaluronan concentration. Twentyfive rabbit dams (term ϭ 31 d) with timed pregnancies were injected s.c. with 0.75 mg of betamethasone or saline (controls) 1 d before delivery. In addition, two dams delivered at 25 d of gestation were injected with 0.75 mg of betamethasone on two consecutive days before delivery. A total of 238 live pups were delivered by preterm cesarean section at 25, 27, 28, or 29 d of gestation and killed immediately. Their lung hyaluronan concentrations were measured with a radiometric assay, and wet/dry lung weight ratios were determined. Lungs of rabbit pups exposed antenatally to betamethasone and delivered at 25 or 27 d of gestation, but not at 28 or 29 d, displayed significantly (p ϭ 0.001 and p ϭ 0.008, respectively) lower hyaluronan concentrations than control pups, accompanied by less intense subepithelial staining for hyaluronan in alveolar walls. There was no significant difference in wet/dry lung weight ratio between pups exposed to one dose of betamethasone and controls. Antenatal corticosteroid exposure lowers the lung hyaluronan concentration in preterm rabbit pups delivered at 25 Antenatal corticosteroid administration to the mother before preterm birth is associated with a reduced incidence of respiratory distress syndrome and a lower neonatal mortality (1-5). This is generally considered to be caused by a steroid-induced increase in surfactant synthesis or release and accelerated morphologic development (6). Accelerated lung cell maturation after steroid exposure has been observed in histologic sections of lungs from rabbits (7). In explant cultures of human fetal lung tissue, increased differentiation (8) and an increase in the capacity of the antioxidant system of the lung to withstand hyperoxia (9) have been noted after exposure to steroids. Antenatally administered corticosteroids also increase the distensibility of the airways (10), an effect at least partially related to the thinning out of the pulmonary interstitium (11). The effects of antenatally administered corticosteroids vary considerably depending on the species, GA at exposure, and steroid dosage (12). The effects of antenatal glucocorticoid administration on fetal lung morphology and function have been most extensively studied in the rabbit and sheep. In preterm rabbits, improved postnatal lung function after maternal corticosteroid administration has been observed even without an increase in the surfactant content of lung tissue or alveoli (13-15).In the lung there are connective tissue fibers in the walls of the pleura, conducting airways, blood vessels, and lymphatics and in the lobular septa, and minute amounts are found in the alveolar walls. Elastic and collagen fibers are equally prominent in most lung connective tissue, except in the alveoli, in which the former predominate. A relative...

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Changes in Hyaluronan Deposition during Early Respiratory Distress Syndrome in Premature Monkeys

Cited by 37 publications

References 18 publications

Hyaluronan Decreases Surfactant Inactivation In Vitro

Hyaluronan Decreases Surfactant Inactivation In Vitro

Lung Water and Proton Magnetic Resonance Relaxation in Preterm and Term Rabbit Pups: Their Relation to Tissue Hyaluronan

Antenatal Betamethasone Administration Decreases the Lung Hyaluronan Concentration in Preterm Rabbit Pups

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