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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- HA:
-
hyaluronan
- PEG:
-
polyethylene glycol
- SA:
-
surface area
- ΔA10:
-
decrease in surface area from the maximum to reach a surface tension of 10 mN/m
References
Clements JA 1997 Lung surfactant: a personal perspective. Annu Rev Physiol 59: 1–21
Avery ME 2000 Surfactant deficiency in hyaline membrane disease. Am J Respir Crit Care Med 161: 074–1075
Suresh GK, Soll RF 2001 Current surfactant use in premature infants. Clin Perinatol 28: 71–694
Gregory TJ, Steinberg KP, Spragg R, Gadek JE, Hyers TM, Longmore WJ, Moxley MA, Cai GZ, Hite RD, Smith RM, Hudson LD, Crim C, Newton P, Mitchell BR, Gold AJ 1997 Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 155: 309–1315
Jobe AH, Ikegami M 1997 Surfactant for acute respiratory distress syndrome. Adv Intern Med 42: 03–230
Taeusch HW 2000 Treatment of acute (adult) respiratory distress syndrome: the holy grail of surfactant therapy. Biol Neonate 77( suppl 1): 1–8
Anzueto A 2002 Surfactant supplementation in the lung. Respir Care Clin N Am 8: 11–236
Notter RH 2000 Lung Surfactants: Basic Science and Clinical Applications. Marcel Dekker, New York, Basic Science and Clinical Applications. Marcel Dekker, New York, pp 207–208
Gupta M, Hernandez-Juviel JM, Waring AJ, Walther FJ 2001 Function and inhibition sensitivity of the N-terminal segment of surfactant protein B (SP-B1–25) in preterm rabbits. Thorax 56: 71–876
Taeusch HW, Lu KW, Goerke J, Clements JA 1999 Nonionic polymers reverse inactivation of surfactant by meconium and other substances. Am J Respir Crit Care Med 159: 391–1395
Kobayashi T, Ohta K, Tashiro K, Nishizuka K, Chen WM, Ohmura S, Yamamoto K 1999 Dextran restores albumin-inhibited surface activity of pulmonary surfactant extract. J Appl Physiol 86: 778–1784
Lu JJ, Cheung WWY, Yu LMY, Policova Z, Li D, Hair ML, Neumann AW 2002 The effect of dextran to restore the activity of pulmonary surfactant inhibited by albumin. Respir Physiol Neurobiol 130: 69–179
Lu KW, Taeusch HW, Robertson B, Goerke J, Clements JA 2000 Polymer-surfactant treatment of meconium-induced acute lung injury. Am J Respir Crit Care Med 162: 23–628
Lu KW, Taeusch HW, Robertson B, Goerke J, Clements JA 2001 Polyethylene glycol/surfactant mixtures improve lung function after HCl and endotoxin lung injuries. Am J Respir Crit Care Med 164: 531–1536
Kobayashi T, Tashiro K, Cui X, Konzaki T, Xu Y, Kabata C, Yamamoto K 2001 Experimental models of acute respiratory distress syndrome: clinical relevance and response to surfactant therapy. Biol Neonate 80( suppl 1): 6–28
Tashiro K, Cui XG, Kobayashi T, Curstedt T, Robertson B 2003 Modified protocols for surfactant therapy in experimental meconium aspiration syndrome. Biol Neonate 83: 9–56
Pasquali-Ronchetti I, Quaglino D, Mori G, Bacchelli B, Ghosh P 1997 Hyaluronan-phospholipid interactions. J Struct Biol 120: 1–10
Sahu SC, Tanswell AK, Lynn WS 1980 Isolation and characterization of glycosaminoglycans secreted by human foetal lung type II pneumocytes in culture. J Cell Sci 42: 83–188
Skinner SJ, Post M, Torday JS, Stiles AD, Smith BT 1987 Characterization of proteoglycans synthesized by fetal rat lung type II pneumonocytes in vitro and the effects of cortisol. Exp Lung Res 12: 53–264
Stratton CJ, Douglas WJ, McAteer JA 1978 The surfactant system of human fetal lung organotypic cultures: ultrastructural preservation by a lipid-carbohydrate retention method. Anat Rec 192: 81–92
Scarpelli EM, Clutario BC, Taylor FA 1967 Preliminary identification of the lung surfactant system. J Appl Physiol 23: 80–886
Nir I, Pease DC 1976 Polysaccharides in lung alveoli. Am J Anat 147: 57–469
Bray BA 2001 The role of hyaluronan in the pulmonary alveolus. J Theor Biol 210: 21–130
Bligh EG, Dyer WJ 1959 A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37: 11–917
Bartlett GR 1959 Phosphorus assay in column chromatography. J Biol Chem 234: 66–468
Boncuk-Dayanikli P, Taeusch HW 1995 Essential and nonessential constituents of exogenous surfactants. In: Robertson B, Taeusch HW (eds) Surfactant Therapy for Lung Disease. Marcel Dekker, New York, pp 217–238
Putz G, Goerke J, Taeusch HW, Clements JA 1994 Comparison of captive and modified pulsating bubble surfactometers. J Appl Physiol 76: 425–1431
Lu KW, Taeusch HW 2001 Polymer effects differ with Survanta, Curosurf and Infasurf. J Investig Med 49: 28A
Bastacky J, Lee CYC, Goerke J, Koushafar H, Yager D, Kenaga L, Speed TP, Chen YA, Clements JA 1995 Alveolar lining layer is thin and continuous: low-temperature scanning electron microscopy of rat lung. J Appl Physiol 79: 615–1628
Ogston AG, Steiner JE 1951 The dimensions of the particle of hyaluronic acid complex in synovial fluid. Biochem J 49: 85–590
Laurent TC 1970 Structure of hyaluronic acid. In: Balazs EA (ed) Chemistry and Molecular Biology of the Intercellular Matrix. Academic Press, London, pp 703–732
Gramling E, Niedermeier W, Holley HL, Pigman W 1963 Some factors affecting the interaction of hyaluronic acid with bovine-plasma albumin. Biochim Biophys Acta 69: 52–558
Gold EW 1980 An interaction of albumin with hyaluronic acid and chondroitin sulfate: a study of affinity chromatography and circular dichroism. Biopolymers 19: 407–1414
Juul SE, Kinsella MG, Jackson JC, Truog WE, Standaert TA, Hodson WA 1994 Changes in hyaluronan deposition during early respiratory distress syndrome in premature monkeys. Pediatr Res 35: 38–243
Juul SE, Kinsella MG, Truog WE, Gibson RL, Redding GJ 1996 Lung hyaluronan decreases during group B streptococcal pneumonia in neonatal piglets. Am J Respir Crit Care Med 153: 567–1570
Savani RC, Hou G, Liu P, Wang C, Simons E, Grimm PC, Stern R, Greenberg AH, DeLisser HM, Khalil N 2000 A role for hyaluronan in macrophage accumulation and collagen deposition after bleomycin-induced lung Injury. Am J Respir Cell Mol Biol 23: 75–484
McKee CM, Penno MB, Cowman M, Burdick MD, Strieter RM, Bao C, Noble PW 1996 Hyaluronan fragments induce chemokine gene expression in alveolar macrophages. J Clin Invest 98: 403–2413
Teder P, Vandivier RW, Jiang D, Liang J, Cohn L, Pure E, Henson PM, Noble PW 2002 Resolution of lung inflammation by CD44. Science 296: 55–158
Cantor JO, Shteyngart B, Cerreta JM, Liu M, Armand G, Turino GM 2000 The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo. Proc Soc Exp Biol Med 225: 5–71
Acknowledgements
We appreciate helpful comments and critical review of the manuscript by Coralie Alonso. We also thank Cynthia Brown for measuring the lipopolysaccharide concentration in the HA.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by National Institutes of Health, Heart, Lung, and Blood Institute Grants RO1 HL 66410 (Department of Pediatrics, University of California, San Francisco) and RO1 HL 24075 (Department of Physiology and the Cardiovascular Research Institute, University of California, San Francisco).
Rights and permissions
About this article
Cite this article
Lu, K., Goerke, J., Clements, J. et al. Hyaluronan Decreases Surfactant Inactivation In Vitro. Pediatr Res 57, 237–241 (2005). https://doi.org/10.1203/01.PDR.0000150726.75308.22
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.PDR.0000150726.75308.22
This article is cited by
-
The unremarkable alveolar epithelial glycocalyx: a thorium dioxide-based electron microscopic comparison after heparinase or pneumolysin treatment
Histochemistry and Cell Biology (2023)
-
What’s new in surfactant?
European Journal of Pediatrics (2007)
