Synaptotagmin II negatively regulates MHC class II presentation by mast cells.
Synaptotagmins (Syts), comprise a gene family of proteins, implicated in the control of protein traffic. Rat basophilic leukemia cells (RBL-2H3), a tumor analogue of mucosal mast cells (MMC), express at least four distinct Syt homologues, including Syt II, Syt III, Syt V and Syt IX. Synaptotagmin II is located at the late/endosomal/lysosomal compartment, where it negatively regulates lysosomal exocytosis. Mast cells may contribute to immune defense mechanisms by presenting MHC class II/antigen complexes and triggering T cell-dependent immune responses. We now demonstrate that RBL-2H3 mast cells, which express reduced levels of Syt II (<5%) by transfection with Syt II antisense cDNA, are able to release MHC class II molecules. We further show that release of both MHC class II molecules and of the lysosomal enzyme cathepsin D is stimulated by lipopolysaccharide (LPS, 1 microg/ml, 48h). We show further that LPS reduces by >40% the level of Syt II expression in both RBL-2H3 and bone marrow-derived mast cells (BMMC). This effect is both dose and time-dependent. These results indicate that Syt II can be down-regulated by external inflammatory signals, resulting in the amplification of mast cell function. Finally, our results implicate Syt II as an important and novel regulator of MHC class II presentation.
Baram
Dana
D
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel.
Peng
Ze
Z
Medalia
Ora
O
Mekori
Yoseph A
YA
Sagi-Eisenberg
Ronit
R
D000818:Animals; D017951:Antigen Presentation; D002402:Cathepsin D / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D005089:Exocytosis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000502:physiology*; D051381:Rats; D050861:Synaptotagmin II; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D050861:Synaptotagmin II; C494263:Syt2 protein, mouse; C494264:Syt2 protein, rat; D002402:Cathepsin D