| First Author | Hazenbos WL | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 9 | Pages | 2825-31 |
| PubMed ID | 15238423 | Mgi Jnum | J:94278 |
| Mgi Id | MGI:3511735 | Doi | 10.1182/blood-2004-02-0671 |
| Citation | Hazenbos WL, et al. (2004) GPI-anchor deficiency in myeloid cells causes impaired FcgammaR effector functions. Blood 104(9):2825-31 |
| abstractText | Signaling by transmembrane immunoglobulin G (IgG)-Fc receptors (FcgammaRs) in response to ligand involves association with membrane microdomains that contain glycosyl phosphatidylinositol (GPI)-anchored proteins. Recent in vitro studies showed enhancement of FcgammaR signaling by forced monoclonal antibody-mediated cocrosslinking with various GPI-anchored proteins. Here, the possibility that GPI-anchored proteins are involved in normal physiologic FcgammaR effector functions in response to a model ligand was studied using myeloid-specific GPI-anchor-deficient mice, generated by Cre-loxP conditional targeting. GPI-anchor-deficient primary myeloid cells exhibited normal FcgammaR expression and binding or endocytosis of IgG-immune complexes (IgG-ICs). Strikingly, after stimulation with IgG-ICs, tumor necrosis factor-alpha release, dendritic cell maturation, and antigen presentation were strongly reduced by GPI-anchor deficiency. Tyrosine phosphorylation of the FcR gamma-chain in response to IgG-IC was impaired in GPI-anchor-deficient cells. Myeloid GPI-anchor deficiency resulted in attenuated in vivo inflammatory processes during IgG-IC-mediated alveolitis. This study provides the first genetic evidence for an essential role of GPI-anchored proteins in physiologic FcgammaR effector functions in vitro and in vivo. |
