A Surface Phase Model of the Alveolar Lining: Ultrastructural Analysis and in vivo Applications
(2002)- Abstract
- In this thesis the relation between lung surfactant structure and functional properties have been studied.
Experimental results show that the alveolar surface is formed by a coherent surface phase with a structure equal to tubular myelin. The properties of this phase may explain certain unresolved issues in lung physiology, e.g., mechanical stability of surfactant during the breathing cycle, the question of free water in the alveolus, and uptake kinetics of pulmonary administered drugs. A surface phase has important consequences in general for the barrier function of the lung, and for host defense.
This surface phase is modeled with a biomathematical approach and is proposed to have a bilayer structure... (More) - In this thesis the relation between lung surfactant structure and functional properties have been studied.
Experimental results show that the alveolar surface is formed by a coherent surface phase with a structure equal to tubular myelin. The properties of this phase may explain certain unresolved issues in lung physiology, e.g., mechanical stability of surfactant during the breathing cycle, the question of free water in the alveolus, and uptake kinetics of pulmonary administered drugs. A surface phase has important consequences in general for the barrier function of the lung, and for host defense.
This surface phase is modeled with a biomathematical approach and is proposed to have a bilayer structure of a minimal surface type, the so-called CLP surface. This structure corresponds to a surfactant bilayer without self-intersections. The functional and structural properties of the CLP surface may explain e.g., the ultra low surface energy of surfactant in vivo, and rapid deformability of the surface phase during breathing.
The role of cholesterol in lung surfactant was studied by X-ray diffraction. It was shown that the presence of cholesterol lowers the crystallization temperature of the surfactant significantly.
During work with a pharmacy-grade lung surfactant, a novel dynamic swelling behavior was observed. During swelling in electrolyte containing water solutions, a dramatic increase of the air-water surface area was seen. In vivo evaluation of this process in an ARDS model was performed, showing significantly higher arterial oxygen levels in rats treated with surfactant in dynamic swelling compared to normal surfactant therapy. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/465163
- author
- Larsson, Marcus LU
- supervisor
- opponent
-
- Professor Gil, Jesus Perez, Dept. Bioquimica, Fac. Biologia, Universidad Complutense de Madrid 28040 Madrid, Spain
- organization
- publishing date
- 2002
- type
- Thesis
- publication status
- published
- subject
- keywords
- X-ray diffraction, cryo-TEM, dynamic swelling, ARDS, surface phase, surfactant replacement therapy, cholesterol, minimal surface, pulmonary surfactant, alveolar surface, Physiology, Fysiologi
- pages
- 103 pages
- publisher
- Marcus Larsson, N. Vallg. 4, 223 62 Lund, Sweden,
- defense location
- Föreläsningssalen, Ingång 73, Plan 1 UMAS, Malmö
- defense date
- 2002-12-06 09:15:00
- ISBN
- 91-628-5448-8
- language
- English
- LU publication?
- yes
- additional info
- Article: I. The alveolar surface structure: Transformation from a liposome-like dispersion into a tetragonal CLP bilayer phase.M. Larsson, K. Larsson, S. Andersson, J. Kakhar, T. Nylander, B. Ninham and P. WollmerJ Dispersion Sci Techn 20 (1999) 1 – 12. Article: II. The alveolar surface is lined by a coherent liquid-crystalline phase.M. Larsson, K. Larsson and P. WollmerProgr Colloid Polym Sci 120 (2002) 28 – 34 Article: III. Enhanced efficacy of porcine lung surfactant extract by utilization of its aqueous swelling dynamics.M. Larsson, J.J. Haitsma, B. Lachmann, K. Larsson, T. Nylander and P, Wollmer.Clin Physiol & Func Im 22 (2002) 39 – 48. Article: IV. The bilayer melting transition in lung surfactant bilayers: role of cholesterol.M. Larsson, K. Larsson, T. Nylander and P. WollmerEur Biophys J in press. Article: V. Human SP-A and a pharmacy-grade porcine lung surfactant extract can be reconstituted into tubular myelin – A comparative structural study of alveolar surfactants using cryo-transmission electron microscopy.M. Larsson, P. Wollmer, J. F. van Iwarden, J. J. Haitsma and B. Lachmann.Submitted. The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Clinical Physiology (013242300), Paediatrics (Lund) (013002000)
- id
- 0b8fb097-ea7d-4d6e-9ddf-68705811c571 (old id 465163)
- date added to LUP
- 2016-04-04 12:14:17
- date last changed
- 2018-11-21 21:09:48
@phdthesis{0b8fb097-ea7d-4d6e-9ddf-68705811c571,
abstract = {{In this thesis the relation between lung surfactant structure and functional properties have been studied.<br/><br>
<br/><br>
Experimental results show that the alveolar surface is formed by a coherent surface phase with a structure equal to tubular myelin. The properties of this phase may explain certain unresolved issues in lung physiology, e.g., mechanical stability of surfactant during the breathing cycle, the question of free water in the alveolus, and uptake kinetics of pulmonary administered drugs. A surface phase has important consequences in general for the barrier function of the lung, and for host defense.<br/><br>
<br/><br>
This surface phase is modeled with a biomathematical approach and is proposed to have a bilayer structure of a minimal surface type, the so-called CLP surface. This structure corresponds to a surfactant bilayer without self-intersections. The functional and structural properties of the CLP surface may explain e.g., the ultra low surface energy of surfactant in vivo, and rapid deformability of the surface phase during breathing.<br/><br>
<br/><br>
The role of cholesterol in lung surfactant was studied by X-ray diffraction. It was shown that the presence of cholesterol lowers the crystallization temperature of the surfactant significantly.<br/><br>
<br/><br>
During work with a pharmacy-grade lung surfactant, a novel dynamic swelling behavior was observed. During swelling in electrolyte containing water solutions, a dramatic increase of the air-water surface area was seen. In vivo evaluation of this process in an ARDS model was performed, showing significantly higher arterial oxygen levels in rats treated with surfactant in dynamic swelling compared to normal surfactant therapy.}},
author = {{Larsson, Marcus}},
isbn = {{91-628-5448-8}},
keywords = {{X-ray diffraction; cryo-TEM; dynamic swelling; ARDS; surface phase; surfactant replacement therapy; cholesterol; minimal surface; pulmonary surfactant; alveolar surface; Physiology; Fysiologi}},
language = {{eng}},
publisher = {{Marcus Larsson, N. Vallg. 4, 223 62 Lund, Sweden,}},
school = {{Lund University}},
title = {{A Surface Phase Model of the Alveolar Lining: Ultrastructural Analysis and in vivo Applications}},
year = {{2002}},
}