GPI-anchoring of GM-CSF results in active membrane-bound and partially shed cytokine

Molecular Immunology
Neil J PolosoP Selvaraj

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) can induce the generation and activation of dendritic cells (DCs), the most potent of antigen presenting cells (APCs). Tumors secreting GM-CSF have been shown to induce strong anti-tumor immune responses. In this report, we have constructed a glycosylphosphatidyl-inositol (GPI) anchored form of GM-CSF (GPI-GM-CSF). This protein subsequently was found expressed on the cell membrane and sensitive to phosphatidyl-inositol-specific phospholipase C (PIPLC), confirming that it is GPI-anchored. However, GM-CSF was also found in the culture supernatant of cells expressing GPI-GM-CSF. Inhibition studies using brefeldin A and para-formaldehyde fixation revealed that GM-CSF found in the supernatant was not secreted, but due to shedding or proteolytic cleavage. Accumulation of GM-CSF in the media from isolated membranes was time and temperature-dependent. The released portion represented 10-15% of all membrane-bound GM-CSF after 72h under culture conditions. GPI-GM-CSF retained functional activity to induce bone marrow cell proliferation and administration of GPI-GM-CSF expressing membranes induced the generation of DCs in vivo. These results demonstrate that GPI-anchored GM-CSF ret...Continue Reading

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Citations

Feb 16, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wen-Yu PanMi-Hua Tao
Nov 19, 2008·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Yufang YangRoys S Sundick
Mar 11, 2015·Nanomedicine : Nanotechnology, Biology, and Medicine·Jaina M PatelPeriasamy Selvaraj
Apr 16, 2015·Oxidative Medicine and Cellular Longevity·Marília BaierleSolange C Garcia
May 16, 2008·Medicinal Research Reviews·Tian-Lu Cheng, Steve Roffler
Oct 13, 2012·Medicinal Research Reviews·Rangaiah ShashidharamurthyPeriasamy Selvaraj
Aug 28, 2014·Acta Biomaterialia·José M Mejía OnetoJulie L Sutcliffe
May 15, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Teena MohanBao-Zhong Wang
Jan 10, 2017·Frontiers in Cellular and Infection Microbiology·Lin-Feng ChengFang-Lin Zhang

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