Document Detail


Function and composition of pulmonary surfactant and surfactant-derived fatty acid profiles are altered in young adults with cystic fibrosis.
MedLine Citation:
PMID:  10893374     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
STUDY OBJECTIVES: To determine whether chronic lung inflammation in young adult patients with cystic fibrosis (CF) alters the composition and function of surfactant and surfactant components in bronchoalveolar secretions. DESIGN: A prospective, descriptive study. SETTING: An adult CF center in a tertiary health-care center. PARTICIPANTS: Thirteen normal volunteer (NV) subjects recruited via local advertising and 15 CF patients recruited from the CF center. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We performed BAL and measured surfactant-associated protein A (SP-A) via enzyme-linked immunosorbent assay in BAL fluid (BALF), and quantitated total phospholipid, phospholipid subclass, and fatty acid subclass content of extracted BALF. We also determined the protein and phospholipid content, SP-A content, and functional characteristics of surfactant isolated from BALF via high-speed centrifugation. The phospholipid-to-protein ratio (milligram/milligram) of surfactant isolated by centrifugation (mean +/- SEM) was 1.01 +/- 0.07 for NV subjects and 2.62 +/- 0.42 for CF patients (p = 0.0001). Minimal surface tension was < 1 dyne.s.cm(-5) in all samples from NV subjects, but 21.9 +/- 0.73 dyne.s.cm(-5) for surfactant from CF patients. Immunoblotting of isolated surfactant revealed a marked decrease in SP-A for CF patients, compared to NV subjects. However, mean concentrations of SP-A in BALF that had not been subjected to high-speed centrifugation to isolate surfactant were not significantly different for CF patients (4.7 +/- 0.8 microgram/mL) vs NV subjects (4.6 +/- 0.2 microgram/mL). Additionally, phospholipid-to-protein ratios (0.32 +/- 0.04 for NV subjects vs 0.10 +/- 0.02 for CF patients; p < 0.0001) in extracted uncentrifuged BALF, and SP-A-to-protein ratios (microgram/milligram) in BALF were significantly depressed (74 +/- 8 for NV subjects vs 16 +/- 3 for CF patients; p < 0.0001). The phospholipid and fatty acid subclass profiles of extracted CF BALF vs NV BALF revealed a decreased mean phosphatidylcholine-to-sphingomyelin ratio (20.7 +/- 10.0 vs 55.2 +/- 8.7; p = 0.002), increased oleic acid content (12.1 +/- 2.3 nmol/mL vs 3.2 +/- 0.9 nmol/mL; p < 0.01), and increased arachidonic acid content (2.2 +/- 0.5 nmol/mL vs 0.6 +/- 0.3 nmol/mL; p < 0.05) for CF patients. CONCLUSIONS: Altered phospholipid-to-protein ratios and phospholipid subclasses, altered surfactant-derived fatty acid profiles, high minimal surface tension, and decreased association of SP-A with lipid components of isolated surfactant indicate that surfactant components are considerably altered and dysfunctional in lower respiratory tract secretions of CF patients. Surfactant composition and function are altered in CF, and the pattern of phospholipid and surfactant-derived fatty acid subclass alterations in CF are characteristic of ongoing lung injury and may depress surfactant function.
Authors:
K C Meyer; A Sharma; R Brown; M Weatherly; F R Moya; J Lewandoski; J J Zimmerman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chest     Volume:  118     ISSN:  0012-3692     ISO Abbreviation:  Chest     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-17     Completed Date:  2000-08-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  164-74     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Wisconsin Medical School, Madison, WI, USA. kcm@medicine.wisc.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Blotting, Western
Bronchoalveolar Lavage Fluid / chemistry
Cystic Fibrosis / metabolism*
Enzyme-Linked Immunosorbent Assay
Humans
Immunoblotting
Phospholipids / chemistry*,  physiology
Prospective Studies
Pulmonary Surfactants / chemistry*,  physiology*
Surface Tension
Chemical
Reg. No./Substance:
0/Phospholipids; 0/Pulmonary Surfactants

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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