학술논문
Cholesterol-mediated surfactant dysfunction is mitigated by surfactant protein A.
Document Type
Academic Journal
Author
Hiansen JQ; Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada. Electronic address: jquahian@gmail.com.; Keating E; Lawson Health Research Institute, London, Ontario, Canada. Electronic address: ekeatin2@uwo.ca.; Aspros A; Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada. Electronic address: aaspros@gmail.com.; Yao LJ; Lawson Health Research Institute, London, Ontario, Canada. Electronic address: jyao@uwo.ca.; Bosma KJ; Department of Medicine, The University of Western Ontario, London, Ontario, Canada. Electronic address: kbosma2@uwo.ca.; Yamashita CM; Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada; Department of Medicine, The University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada. Electronic address: cyamash@uwo.ca.; Lewis JF; Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada; Department of Medicine, The University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada. Electronic address: jflewis@uwo.ca.; Veldhuizen RA; Department of Physiology & Pharmacology, The University of Western Ontario, London, Ontario, Canada; Department of Medicine, The University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada. Electronic address: rveldhui@uwo.ca.
Source
Publisher: Elsevier Pub. Co Country of Publication: Netherlands NLM ID: 0217513 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-3002 (Print) Linking ISSN: 00063002 NLM ISO Abbreviation: Biochim Biophys Acta Subsets: MEDLINE
Subject
Language
English
ISSN
0006-3002
Abstract
The ability of pulmonary surfactant to reduce surface tension at the alveolar surface is impaired in various lung diseases. Recent animal studies indicate that elevated levels of cholesterol within surfactant may contribute to its inhibition. It was hypothesized that elevated cholesterol levels within surfactant inhibit human surfactant biophysical function and that these effects can be reversed by surfactant protein A (SP-A). The initial experiment examined the function of surfactant from mechanically ventilated trauma patients in the presence and absence of a cholesterol sequestering agent, methyl-β-cyclodextrin. The results demonstrated improved surface activity when cholesterol was sequestered in vitro using a captive bubble surfactometer (CBS). These results were explored further by reconstitution of surfactant with various concentrations of cholesterol with and without SP-A, and testing of the functionality of these samples in vitro with the CBS and in vivo using surfactant depleted rats. Overall, the results consistently demonstrated that surfactant function was inhibited by levels of cholesterol of 10% (w/w phospholipid) but this inhibition was mitigated by the presence of SP-A. It is concluded that cholesterol-induced surfactant inhibition can actively contribute to physiological impairment of the lungs in mechanically ventilated patients and that SP-A levels may be important to maintain surfactant function in the presence of high cholesterol within surfactant.
(Copyright © 2014 Elsevier B.V. All rights reserved.)
(Copyright © 2014 Elsevier B.V. All rights reserved.)