title: Transient exposure of pulmonary surfactant to hyaluronan promotes structural and compositional transformations into a highly active state.
abstract: Pulmonary surfactant is a lipid-protein complex that lowers surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to collapse alveoli. Dysfunction of surfactant is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome where naturally occurring surfactant-inhibitory agents such as serum, meconium, or cholesterol reach the lung. We analyzed the effect of hyaluronan (HA) on the structure and surface behavior of pulmonary surfactant to understand the mechanism for HA-promoted surfactant protection in the presence of inhibitory agents. In particular, we found that HA affects structural properties such as the aggregation state of surfactant membranes and the size, distribution, and order/packing of phase-segregated lipid domains. These effects do not require a direct interaction between surfactant complexes and HA and are accompanied by a compositional reorganization of large surfactant complexes that become enriched with saturated phospholipid species. HA-exposed surfactant reaches very high efficiency in terms of rapid and spontaneous adsorption of surfactant phospholipids at the air-liquid interface and shows significantly improved resistance to inactivation by serum or cholesterol. We propose that physical effects pertaining to the formation of a meshwork of interpenetrating HA polymer chains are responsible for the changes in surfactant structure and composition that enhance surfactant function and, thus, resistance to inactivation. The higher resistance of HA-exposed surfactant to inactivation persists even after removal of the polymer, suggesting that transient exposure of surfactant to polymers like HA could be a promising strategy for the production of more efficient therapeutic surfactant preparations.
authors: From the Departamento de Bioquimica y Biologia Molecular, Facultad de Biologia, Universidad Complutense, 28040 Madrid, Spain.
authors: Elena
authors: E
authors: Lopez-Rodriguez
authors: Antonio
authors: A
authors: Cruz
authors: Ralf P
authors: RP
authors: Richter
authors: H William
authors: HW
authors: Taeusch
authors: Jesús
authors: J
authors: Pérez-Gil
mesh_terms: D000327:Adsorption; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry*; D013499:Surface Properties; D013552:Swine; D013816:Thermodynamics
chemical_list: D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D006820:Hyaluronic Acid
keywords: Air-Liquid Interface; Hyaluronate; Membrane Bilayer; Membrane Biophysics; Phospholipid Vesicle; Pulmonary Surfactant; Pulmonary Surfactant Inhibition
references: Langmuir. 2006 Apr 11;22(8):3497-505
references: 16584220
references: J Biol Chem. 2004 Sep 24;279(39):40715-22
references: 15231828
references: Biochim Biophys Acta. 2010 Apr;1798(4):801-28
references: 20026298
references: Biophys J. 2013 Jan 8;104(1):146-55
references: 23332067
references: Biomacromolecules. 2012 May 14;13(5):1466-77
references: 22455455
references: Biochem J. 2011 Sep 15;438(3):555-64
references: 21679160
references: Biophys J. 2011 Feb 2;100(3):646-655
references: 21281579
references: Inflammation. 1980 Mar;4(1):107-12
references: 7390611
references: Anal Chem. 2011 Dec 1;83(23):8838-48
references: 21939220
references: Biophys J. 2005 Sep;89(3):1769-79
references: 15923228
references: J Am Chem Soc. 2007 May 2;129(17):5306-7
references: 17408270
references: Eur J Pharmacol. 2007 Jul 30;568(1-3):1-15
references: 17543939
references: Biophys J. 2009 Sep 2;97(5):1381-9
references: 19720026
references: J Theor Biol. 2001 May 7;210(1):121-30
references: 11343436
references: Langmuir. 2012 Feb 14;28(6):3206-16
references: 22216832
references: Pediatr Res. 2005 Feb;57(2):237-41
references: 15585679
references: Biochem J. 1988 Sep 1;254(2):489-93
references: 2845953
references: Physiol Rev. 1978 Jan;58(1):255-315
references: 414242
references: Am J Respir Crit Care Med. 2002 Feb 15;165(4):475-80
references: 11850339
references: Biophys J. 2012 Jul 3;103(1):L10-2
references: 22828349
references: Biorheology. 2007;44(2):59-74
references: 17538199
references: Pediatr Res. 2005 Nov;58(5):913-8
references: 16183815
references: Lipids. 1966 Jan;1(1):85-6
references: 17805690
references: Chem Phys Lipids. 2008 Aug;154(2):115-9
references: 18405664
references: Respir Physiol Neurobiol. 2010 Aug 31;173 Suppl:S55-64
references: 20206718
references: Colloids Surf B Biointerfaces. 2008 Apr 1;62(2):243-9
references: 18065212
references: Cochrane Database Syst Rev. 2007 Jul 18;(3):CD002054
references: 17636695
references: Biochim Biophys Acta. 2012 May;1818(5):1225-34
references: 22206628
references: Biorheology. 2009;46(1):31-43
references: 19252226
references: Biophys J. 2012 Feb 22;102(4):777-86
references: 22385848
references: Biochim Biophys Acta. 1994 Aug 18;1200(3):281-90
references: 8068714
references: Biophys J. 2005 Sep;89(3):1621-9
references: 16006630
references: Am J Physiol. 1989 Dec;257(6 Pt 1):L379-84
references: 2481983
references: Biophys J. 2010 Apr 21;98(8):1549-57
references: 20409474
references: Immunol Cell Biol. 1996 Apr;74(2):A1-7
references: 8724014
references: Carbohydr Res. 2005 Apr 11;340(5):791-809
references: 15780246
references: Biochim Biophys Acta. 2009 May;1788(5):1033-43
references: 19366599
references: Science. 1996 Jul 19;273(5273):330-2
references: 8662513
references: Biochim Biophys Acta. 1998 Nov 19;1408(2-3):203-17
references: 9813327
references: Biorheology. 1993 Jan-Feb;30(1):31-41
references: 8374100
references: Am J Respir Crit Care Med. 2003 May 1;167(9):1169-75
references: 12714341
references: Biochim Biophys Acta. 2009 Mar;1788(3):632-7
references: 19366601
references: J Biol Chem. 2010 Sep 24;285(39):30170-80
references: 20663884
references: Biophys J. 2012 Oct 3;103(7):1451-9
references: 23062337
references: Biochem J. 1992 Mar 1;282 ( Pt 2):467-70
references: 1546961
references: Am J Respir Crit Care Med. 2011 Apr 15;183(8):1055-61
references: 21148720
references: Biochim Biophys Acta. 1998 Nov 19;1408(2-3):180-202
references: 9813315
references: Biophys J. 2009 Nov 18;97(10):2736-45
references: 19917227
references: Q Rev Biophys. 2001 May;34(2):105-267
references: 11771120
references: Langmuir. 2010 Jan 19;26(2):1029-34
references: 19736978