Cigarette smoke inhibits efferocytosis via deregulation of sphingosine kinase signaling: reversal with exogenous S1P and the S1P analogue FTY720

Journal of Leukocyte Biology
Hai B TranSandra Hodge

Abstract

Alveolar macrophages from chronic obstructive pulmonary disease patients and cigarette smokers are deficient in their ability to phagocytose apoptotic bronchial epithelial cells (efferocytosis). We hypothesized that the defect is mediated via inhibition of sphingosine kinases and/or their subcellular mislocalization in response to cigarette smoke and can be normalized with exogenous sphingosine-1-phosphate or FTY720 (fingolimod), a modulator of sphingosine-1-phosphate signaling, which has been shown to be clinically useful in multiple sclerosis. Measurement of sphingosine kinase 1/2 activities by [(32)P]-labeled sphingosine-1-phosphate revealed a 30% reduction of sphingosine kinase 1 (P < 0.05) and a nonsignificant decrease of sphingosine kinase 2 in THP-1 macrophages after 1 h cigarette smoke extract exposure. By confocal analysis macrophage sphingosine kinase 1 protein was normally localized to the plasma membrane and cytoplasm and sphingosine kinase 2 to the nucleus and cytoplasm but absent at the cell surface. Cigarette smoke extract exposure (24 h) led to a retraction of sphingosine kinase 1 from the plasma membrane and sphingosine kinase 1/2 clumping in the Golgi domain. Selective inhibition of sphingosine kinase 2 with 2...Continue Reading

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Citations

Jun 10, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Eugene RoscioliSandra Hodge
Sep 23, 2019·Respirology : Official Journal of the Asian Pacific Society of Respirology·Miranda P WeenSandra J Hodge
Jun 9, 2018·International Journal of Environmental Research and Public Health·Agnieszka StrzelakWojciech Feleszko
Aug 6, 2019·Frontiers in Immunology·Andreas WeigertBernhard Brüne
Sep 9, 2018·Scientific Reports·Rhys HamonSandra Hodge
Aug 29, 2019·Frontiers in Pharmacology·Simone ArientiIan Dransfield
Apr 20, 2018·Journal of Immunology Research·Theodore S KapellosJoachim L Schultze
Jun 5, 2020·Lipids in Health and Disease·Christina W AgudeloItsaso Garcia-Arcos
Feb 20, 2021·Scientific Reports·Miranda P WeenSandra J Hodge
Dec 3, 2021·Therapeutic Advances in Respiratory Disease·Patrick F AsareSandra Hodge

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