Lacto-N-fucopentaose III, a Pentasaccharide, Prolongs Heart Transplant Survival
| Autor: | Hans W. Sollinger, William J. Burlingham, Jose R. Torrealba, Partha Dutta, Debra A. Hullett, Donald A. Harn, Drew A. Roenneburg |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Time Factors medicine.medical_treatment CD11c T-Lymphocytes Regulatory B7-H1 Antigen Mice Immune system Polysaccharides Pregnancy PD-L1 medicine Animals Transplantation Homologous Lymph node Heart transplantation Transplantation Membrane Glycoproteins biology business.industry Graft Survival FOXP3 Amino Sugars Forkhead Transcription Factors Dendritic Cells Macrophage Activation Mice Inbred C57BL medicine.anatomical_structure Animals Newborn Mice Inbred DBA Immunology B7-1 Antigen Macrophages Peritoneal biology.protein Heart Transplantation Female Lymph Peptides business Immunosuppressive Agents |
| Zdroj: | Transplantation. 90:1071-1078 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/tp.0b013e3181f8f296 |
| Popis: | Background. Lacto-N-fucopentaose III (LNFPIII) is a pentasaccharide containing the Lewis x trisaccharide that is found on schistosome eggs and in breast milk. LNFPIII conjugates suppress host immune responses and have therapeutic efficacy in mouse models of psoriasis and type 1 diabetes. Methods. We used nonvascularized neonatal ear-heart transplantation and heterotopic vascularized heart transplantation models to evaluate immunosuppressive effects of LNFPIII and subsequently analyzed the mechanism. Results. We found that administration of LNFPIII conjugates prolonged median graft survival by 80% when 1-day-old DBA/2 hearts were transplanted into ears of B6 mice. A similar graft prolongation was observed in a fully vascularized heterotopic heart transplantation model (DBA/2 into B6), No prolongation was observed with carrier protein (human serum albumin [HSA] or dextran) alone. We found increased programmed death ligand 1 (PD-L1) expression on F4/80 + macrophages, CD4 + T cells, and CD11b + CD11c + (myeloid) dendritic cells, and increased arginase1 and Ym1 expression, typical of alternatively activated macrophages, in the draining (cervical) lymph node cells. We found accumulation of Foxp3 + regulatory T cells (Tregs) in the lymph nodes draining donor hearts, suggesting a possible role of Treg induction in graft prolongation. Anti-PD-L1 antibody treatment abrogated LNFPIII-mediated the graft survival benefit and Treg accumulation. LNFPIII-treated macrophages had increased PD-L expression and significantly prolonged DBA/2 allograft survival when injected intraperitoneally into B6 recipient mice. Conclusions. LNFPIII prolongs fully allogeneic graft survival in both vascularized and nonvascularized allograft transplantation models. The mechanism of graft prolongation seems to involve both alternatively activated PDL-1 + macrophages and recruitment of Foxp3 + Treg cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|