title: Localized lipidomics in cystic fibrosis: TOF-SIMS imaging of lungs from Pseudomonas aeruginosa-infected mice.
abstract: A consistent body of research has linked cystic fibrosis (CF) with variations in the tissue and fluid content in a number of lipid molecules. However, little is known about the spatial localization of those variations. We have recently applied TOF-SIMS mass spectrometry imaging to detect differential lipid signatures at the colon epithelium between normal and cftr-/- mice. In the present work we have used this technology to investigate potential differences in the spatial distribution of lipids due to Pseudomonas aeruginosa (P.a.) infection in mouse lung expressing or not cftr. Wild-type and exon 10 cftr knockout mice were subjected to intranasal infection with a clinical strain of P.a. Lung cryosections from infected and non-infected mice were subjected to cluster TOF-SIMS analysis in the negative ion mode. We observed a highly specific localization of a phosphoinositol fragment ion at m/z 299.1 in bronchial epithelium. Using this ion to delineate a region of interest, we studied the relative abundance of ions below m/z 1500. We found a significant increase in m/z 465.4 (identified as cholesteryl sulfate) in cftr-/- epithelium and in response to bacterial infection, as well as a decrease in most carboxylic ions. In conclusion, the m/z 299.1 ion can be used as a marker of bronchial epithelium, where P.a. infection leads to increased presence of cholesteryl sulfate in this tissue. TOF-SIMS imaging reveals as a valuable tool for the study of respiratory epithelium.
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors: Nicolas
authors: N
authors: Desbenoit
authors: INSERM, U 845, 75015 Paris, France; Université Paris Descartes, 75015 Paris, France.
authors: Emilie
authors: E
authors: Saussereau
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors: Claudia
authors: C
authors: Bich
authors: INSERM, U 845, 75015 Paris, France; Université Paris Descartes, 75015 Paris, France.
authors: Matthieu
authors: M
authors: Bourderioux
authors: INSERM, U 845, 75015 Paris, France; Université Paris Descartes, 75015 Paris, France.
authors: Janine
authors: J
authors: Fritsch
authors: INSERM, U 845, 75015 Paris, France; Université Paris Descartes, 75015 Paris, France.
authors: Aleksander
authors: A
authors: Edelman
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors: Alain
authors: A
authors: Brunelle
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France; INSERM, U 845, 75015 Paris, France; Université Paris Descartes, 75015 Paris, France. Electronic address: Mario.ollero@inserm.fr.
authors: Mario
authors: M
authors: Ollero
mesh_terms: D000818:Animals; D002788:Cholesterol Esters / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency; D004195:Disease Models, Animal; D050356:Lipid Metabolism; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011552:Pseudomonas Infections / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
chemical_list: D002788:Cholesterol Esters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C007045:cholesteryl sulfate
keywords: Bronchial epithelium; Cholesteryl sulfate; Mass spectrometry; Phosphoinositol; TOF-SIMS