Plasma membrane abundance dictates phagocytic capacity and functional crosstalk in myeloid cells.

Autor: Winer BY; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA.; Department of Microbiology and Immunology, University of California San Francisco; San Francisco, CA, USA.; Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA.; Department of Biochemistry and Biophysics, University of California San Francisco; San Francisco, CA, USA., Settle AH; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Yakimov AM; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Jeronimo C; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Lazarov T; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Tipping M; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Saoi M; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Sawh A; New York Structural Biology Center; New York, NY, USA., Sepp AL; Department of Biomedical Engineering, Columbia University; New York, NY, USA., Galiano M; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Wong YY; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Perry JSA; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Geissmann F; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Cross J; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Zhou T; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Kam LC; Department of Biomedical Engineering, Columbia University; New York, NY, USA., Pasoli HA; Electron Microscopy Resource Center, The Rockefeller University; New York, NY, USA., Hohl T; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA., Cyster JG; Department of Microbiology and Immunology, University of California San Francisco; San Francisco, CA, USA.; Howard Hughes Medical Institute; Chevy Chase, MD, USA., Weiner OD; Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA.; Department of Biochemistry and Biophysics, University of California San Francisco; San Francisco, CA, USA., Huse M; Immunology Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 13. Date of Electronic Publication: 2023 Sep 13.
DOI: 10.1101/2023.09.12.556572
Abstrakt: Professional phagocytes like neutrophils and macrophages tightly control what they eat, how much they eat, and when they move after eating. We show that plasma membrane abundance is a key arbiter of these cellular behaviors. Neutrophils and macrophages lacking the G-protein subunit Gb4 exhibit profound plasma membrane expansion due to enhanced production of sphingolipids. This increased membrane allocation dramatically enhances phagocytosis of bacteria, fungus, apoptotic corpses, and cancer cells. Gb4 deficient neutrophils are also defective in the normal inhibition of migration following cargo uptake. In Gb4 knockout mice, myeloid cells exhibit enhanced phagocytosis of inhaled fungal conidia in the lung but also increased trafficking of engulfed pathogens to other organs. These results reveal an unexpected, biophysical control mechanism lying at the heart of myeloid functional decision-making.
Databáze: MEDLINE