Lacto-N-fucopentaose III, a pentasaccharide, prolongs heart transplant survival

Partha Dutta, Debra A. Hullett, Drew A. Roenneburg, Jose R. Torrealba, Hans W. Sollinger, Donald A. Harn, William J. Burlingham

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. Lacto-N-fucopentaose III (LNFPIII) is a pentasaccharide containing the LewisX 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+ Tcells, 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-L1 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.

Original languageEnglish (US)
Pages (from-to)1071-1078
Number of pages8
JournalTransplantation
Volume90
Issue number10
DOIs
StatePublished - Nov 27 2010

Fingerprint

Transplants
Graft Survival
Heart Transplantation
Macrophages
Regulatory T-Lymphocytes
Ligands
Allografts
Ear
Lymph Nodes
Heterotopic Transplantation
Trisaccharides
Human Milk
Myeloid Cells
Immunosuppressive Agents
lacto-N-fucopentaose III
Dextrans
Type 1 Diabetes Mellitus
Psoriasis
Serum Albumin
Dendritic Cells

Keywords

  • Alternatively activated macrophages
  • LNFPIII
  • PD-L1

ASJC Scopus subject areas

  • Transplantation

Cite this

Dutta, P., Hullett, D. A., Roenneburg, D. A., Torrealba, J. R., Sollinger, H. W., Harn, D. A., & Burlingham, W. J. (2010). Lacto-N-fucopentaose III, a pentasaccharide, prolongs heart transplant survival. Transplantation, 90(10), 1071-1078. https://doi.org/10.1097/TP.0b013e3181f8f296

Lacto-N-fucopentaose III, a pentasaccharide, prolongs heart transplant survival. / Dutta, Partha; Hullett, Debra A.; Roenneburg, Drew A.; Torrealba, Jose R.; Sollinger, Hans W.; Harn, Donald A.; Burlingham, William J.

In: Transplantation, Vol. 90, No. 10, 27.11.2010, p. 1071-1078.

Research output: Contribution to journalArticle

Dutta, P, Hullett, DA, Roenneburg, DA, Torrealba, JR, Sollinger, HW, Harn, DA & Burlingham, WJ 2010, 'Lacto-N-fucopentaose III, a pentasaccharide, prolongs heart transplant survival', Transplantation, vol. 90, no. 10, pp. 1071-1078. https://doi.org/10.1097/TP.0b013e3181f8f296
Dutta, Partha ; Hullett, Debra A. ; Roenneburg, Drew A. ; Torrealba, Jose R. ; Sollinger, Hans W. ; Harn, Donald A. ; Burlingham, William J. / Lacto-N-fucopentaose III, a pentasaccharide, prolongs heart transplant survival. In: Transplantation. 2010 ; Vol. 90, No. 10. pp. 1071-1078.
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AU - Hullett, Debra A.

AU - Roenneburg, Drew A.

AU - Torrealba, Jose R.

AU - Sollinger, Hans W.

AU - Harn, Donald A.

AU - Burlingham, William J.

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