Cholesteryl esters are elevated in the lipid fraction of bronchoalveolar lavage fluid collected from pediatric cystic fibrosis patients.
BACKGROUND
Host-derived lipids including cholesteryl esters (CEs) such as cholesteryl linoleate have emerged as important antibacterial effectors of innate immunity in the airways and cholesteryl linoleate has been found elevated in the context of inflammation. Cystic fibrosis (CF) patients suffer from chronic infection and severe inflammation in the airways. Here, we identified and quantified CEs in bronchoalveolar lavage fluid (BALF) from CF patients and non-CF disease controls, and tested whether CE concentrations are linked to the disease.


METHODS
CEs in BALF from 6 pediatric subjects with CF and 7 pediatric subjects with non-CF chronic lung disease were quantified by mass spectral analysis using liquid chromatography coupled with tandem mass spectrometry and multiple reaction monitoring. BALFs were also examined for total lipid, total protein, albumin, and, as a marker for inflammation, human neutrophil peptide (HNP) 1-3 concentrations. Statistical analysis was conducted after log 10 transformation of the data.


RESULTS
Total lipid/protein ratio was reduced in CF BALF (p = 0.018) but the concentrations of CEs, including cholesteryl linoleate, were elevated in the total lipid fraction in CF BALF compared to non-CF disease controls (p < 0.050). In addition, the concentrations of CEs and HNP1-3 correlated with one another (p < 0.050).


CONCLUSIONS
The data suggests that the lipid composition of BALF is altered in CF with less total lipid relative to protein but with increased CE concentrations in the lipid fraction, likely contributed by inflammation. Future longitudinal studies may reveal the suitability of CEs as a novel biomarker for CF disease activity which may provide new information on the lipid mediated pathophysiology of the disease.
Department of Biological Sciences, California State University Los Angeles, Los Angeles, California, United States of America.
Daniel C
DC
Ma
Pasarow Mass Spectrometry Laboratory, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of America.
Alexander J
AJ
Yoon
Pasarow Mass Spectrometry Laboratory, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of America.
Kym F
KF
Faull
Department of Biological Sciences, California State University Los Angeles, Los Angeles, California, United States of America.
Robert
R
Desharnais
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Edith T
ET
Zemanick
Department of Biological Sciences, California State University Los Angeles, Los Angeles, California, United States of America.
Edith
E
Porter
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002788:Cholesterol Esters / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000032:analysis; D013048:Specimen Handling
D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D002788:Cholesterol Esters; D011506:Proteins