Sphingosine-1-phosphate lyase is expressed by CD68+ cells on the parenchymal side of marginal reticular cells in human lymph nodes

Eur J Immunol. 2014 Aug;44(8):2425-36. doi: 10.1002/eji.201344158. Epub 2014 Jun 12.


Lymph nodes (LNs) form the intersection between the vascular and lymphatic systems. Lymphocytes and antigen-presenting cells (APCs) traffic between these systems, but the barriers crossed during this trafficking in human LNs are poorly defined. We identified a population of cells in human LNs that lines the boundary between the parenchyma and lymphatic sinuses, consistent with descriptions of marginal reticular cells (MRCs) in murine LNs. Human MRCs are CD141(high) podoplanin(+), CD90(+), ICAM1(+), and VCAM1(+) but lack endothelial and hematopoietic cell markers, or alpha-smooth muscle actin. We then examined expression of the enzyme sphingosine-1-phosphate (S1P) lyase (SGPL1) relative to the boundary defined by MRCs. SGPL1 expression was almost exclusively restricted to cells on the parenchymal side of MRCs, consistent with a role in maintaining the S1P gradient between the sinuses and the parenchyma. Surprisingly the cells expressing SGPL1 in the parenchyma were CD68(+) APCs. CD68(+) APCs generated from human monocytes were able to internalize and irreversibly degrade S1P, and this activity was inhibited by the S1P analogue FTY720. This work provides a map of the key structures at the boundary where human lymphocytes egress into sinuses, and identifies a novel potential mechanism for the activity of S1P analogues in humans.

Keywords: FTY720; Lymph node; Lymphocyte egress; Marginal reticular cells; Sphingosine 1-phosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde-Lyases / biosynthesis*
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Cell Movement / physiology
  • Humans
  • Lymph Nodes / cytology
  • Lymph Nodes / enzymology*
  • Lymph Nodes / metabolism
  • Lymphatic System / cytology
  • Lymphatic System / enzymology
  • Lymphatic System / metabolism
  • Lymphocytes / cytology
  • Lymphocytes / enzymology
  • Lymphocytes / metabolism
  • Lysophospholipids / metabolism
  • Mesophyll Cells / cytology
  • Mesophyll Cells / enzymology*
  • Mesophyll Cells / metabolism
  • Monocytes / metabolism
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Lysophospholipids
  • sphingosine 1-phosphate
  • Aldehyde-Lyases
  • sphingosine 1-phosphate lyase (aldolase)
  • Sphingosine