Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies

J Vasc Res. 2000 Sep-Oct;37(5):417-25. doi: 10.1159/000025758.


Endothelial-cell-specific molecule 1 (ESM-1) is a recently identified endothelial cell molecule. As ESM-1 mRNA is preferentially expressed in human lung and kidney tissues, and as ESM-1 mRNA expression is regulated by inflammatory cytokines, ESM-1 is thought to play a role in the vascular contribution to organ-specific inflammation. In order to define its behavior, mouse anti-ESM-1 monoclonal antibodies were developed, and three distinct epitopes were mapped, which allowed development of a specific ELISA assay, immunohistological staining and immunoblot analysis. Here, we demonstrate that ESM-1 is present in cell lysates of human endothelial cells (human umbilical vein endothelial cells) with an apparent molecular weight of 20 kD. In contrast, the secreted form of ESM-1 is shifted to an apparent molecular weight of 50 kD, indicating that the secreted form of ESM-1 is posttranslationally modified. By ELISA, we show that the secretion of ESM-1 is significantly enhanced in the presence of TNFalpha. In contrast, the spontaneous as well as TNFalpha-induced secretion of ESM-1 is strongly inhibited by IFNgamma. Moreover, ESM-1 was detected in the serum of healthy subjects at an average concentration of 1.08 ng/ml, and we demonstrated that the serum level of ESM-1 is dramatically increased in patients presenting a septic shock. Analysis of ESM-1 expression in normal human tissues by immunohistochemistry showed that ESM-1 is localized in the vascular network, but also in the bronchial and renal epithelia. Our results demonstrate that ESM-1 is mainly expressed in the vascular endothelium both in vitro and in vivo, but also by different epithelia. ESM-1 may represent a new marker of endothelial cell activation, and may have a functional role in endothelium-dependent pathological disorders.

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Blotting, Western
  • Endothelium, Vascular / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Epithelium / chemistry
  • Epitope Mapping
  • Female
  • Graft Rejection
  • Humans
  • Immunosorbent Techniques
  • Kidney / blood supply
  • Kidney Transplantation
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Proteins*
  • Proteins / analysis*
  • Proteins / immunology
  • Proteoglycans*
  • Sepsis / blood
  • Umbilical Veins


  • Antibodies, Monoclonal
  • ESM1 protein, human
  • Neoplasm Proteins
  • Proteins
  • Proteoglycans