PMID- 10447750 OWN - NLM STAT- MEDLINE DCOM- 20000404 LR - 20190513 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 97 IP - 2 DP - 1999 Jun TI - FcepsilonRI-mediated antigen endocytosis turns interferon-gamma-treated mouse mast cells from inefficient into potent antigen-presenting cells. PG - 333-40 AB - Previous studies in our laboratory have shown that bone-marrow-derived mast cells (BMMC) could present immunogenic peptides, from soluble antigens endocytosed through fluid phase, only if they were subjected to a 48-hr treatment with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In contrast to GM-CSF, interferon-gamma (IFN-gamma) which highly upregulates major histocompatibility complex (MHC) class II expression, completely inhibits the generation of immunogenic peptides. We have used this model to study the role of FcepsilonRI-mediated antigen internalization in the regulation of the antigen-presenting function of IFN-gamma-treated mast cells. Here, we report that FcepsilonRI can reverse the IFN-gamma-treated mast cells from inefficient to highly efficient antigen-presenting cells. Inhibition of the antigen presenting capacity by piceatannol, a protein tyrosine kinase (PTK) syk inhibitor, indicates that this is an active process resulting from immunoglobulin E (IgE)-antigen-FcepsilonRI engagement which involves tyrosines found in the immunoreceptor tyrosine-based activation motif (ITAM) embedded in the cytoplasmic tail of the FcepsilonRI beta and gamma chains. Antigen-presenting function was also shown to require the activation of phosphatidyl inositol 3 (PI3) kinase, downstream of PTK syk phosphorylation, since this activity was completely blocked by wortmannin, a PI3 kinase inhibitor. These data suggest that signalling generated by FcepsilonRI provides mast cells with IgE-mediated enhanced antigen presentation to T cells and emphasize a so far unknown immunoregulatory mast-cell function that might take place in inflammatory sites. FAU - Tkaczyk, C AU - Tkaczyk C AD - Unite d'immuno-allergie, Institut Pasteur, Paris, France. FAU - Villa, I AU - Villa I FAU - Peronet, R AU - Peronet R FAU - David, B AU - David B FAU - Mecheri, S AU - Mecheri S LA - eng PT - Journal Article PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Dinitrophenols) RN - 0 (Haptens) RN - 0 (Receptors, IgE) RN - 0 (Recombinant Proteins) RN - 0 (dinitrophenol-ovalbumin) RN - 37341-29-0 (Immunoglobulin E) RN - 82115-62-6 (Interferon-gamma) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - Antigen-Presenting Cells/*immunology MH - Bone Marrow/immunology MH - Dinitrophenols/immunology MH - Endocytosis/*immunology MH - Haptens/immunology MH - Hydrogen-Ion Concentration MH - Immunoglobulin E/immunology MH - Interferon-gamma/*immunology MH - Lysosomes/immunology MH - Mast Cells/*immunology MH - Mice MH - Mice, Inbred DBA MH - Ovalbumin/immunology MH - Receptors, IgE/*immunology MH - Recombinant Proteins PMC - PMC2326822 EDAT- 1999/08/14 10:00 MHDA- 2001/07/04 10:01 PMCR- 2000/06/01 CRDT- 1999/08/14 10:00 PHST- 1999/08/14 10:00 [pubmed] PHST- 2001/07/04 10:01 [medline] PHST- 1999/08/14 10:00 [entrez] PHST- 2000/06/01 00:00 [pmc-release] AID - imm789 [pii] AID - 10.1046/j.1365-2567.1999.00789.x [doi] PST - ppublish SO - Immunology. 1999 Jun;97(2):333-40. doi: 10.1046/j.1365-2567.1999.00789.x.