Abstract

Lipids play a central role in lung physiology and pathology; however, a comprehensive lipidomic characterization of human pulmonary cells relevant to disease has not been performed. The cells involved in lung host defense, including alveolar macrophages (AMs), bronchial epithelial cells (BECs), and alveolar type II cells (ATIIs), were isolated from human subjects and lipidomic analysis by LC-MS and LC-MS/MS was performed. Additionally, pieces of lung tissue from the same donors were analyzed by MALDI imaging MS in order to determine lipid localization in the tissue. The unique distribution of phospholipids in ATIIs, BECs, and AMs from human subjects was accomplished by subjecting the large number of identified phospholipid molecular species to univariant statistical analysis. Specific MALDI images were generated based on the univariant statistical analysis data to reveal the location of specific cell types within the human lung slice. While the complex composition and function of the lipidome in various disease states is currently poorly understood, this method could be useful for the characterization of lipid alterations in pulmonary disease and may aid in a better understanding of disease pathogenesis.

Highlights

  • Lipids play a central role in lung physiology and pathology; a comprehensive lipidomic characterization of human pulmonary cells relevant to disease has not been performed

  • A well-known example is that of leukotrienes and prostaglandins, which are lipid mediators derived from enzymatic metabolism of arachidonic acid (AA) released from phospholipids in cell membranes

  • Pulmonary cells of interest in inflammatory disease pathogenesis, such as asthma, COPD, and cystic fibrosis, are those involved in host defense and responsible for Abbreviations: AA, arachidonic acid; AM, alveolar macrophage; ATII, alveolar type II cell; BEC, bronchial epithelial cell; collision-induced dissociation (CID), collisioninduced dissociation; COX, cyclooxygenase; DHAP, 2,6-dihydroxyacetophenone; IMS, imaging MS; LO, lipoxygenase; mOCT, modified OCT; NP, normal phase; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PPG, polypropylene glycol; PS, phosphatidylserine

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Summary

Introduction

Lipids play a central role in lung physiology and pathology; a comprehensive lipidomic characterization of human pulmonary cells relevant to disease has not been performed. Pulmonary cells of interest in inflammatory disease pathogenesis, such as asthma, COPD, and cystic fibrosis, are those involved in host defense and responsible for Abbreviations: AA, arachidonic acid; AM, alveolar macrophage; ATII, alveolar type II cell; BEC, bronchial epithelial cell; CID, collisioninduced dissociation; COX, cyclooxygenase; DHAP, 2,6-dihydroxyacetophenone; IMS, imaging MS; LO, lipoxygenase; mOCT, modified OCT; NP, normal phase; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PPG, polypropylene glycol; PS, phosphatidylserine

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