Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule-1 (VCAM-1)

Clin Exp Immunol. 1996 Feb;103(2):259-67. doi: 10.1046/j.1365-2249.1996.d01-626.x.


VCAM-1 was first identified as an adhesion molecule induced on human endothelial cells (HEC) by inflammatory cytokines such as IL-1, tumour necrosis factor (TNF), and lipopolysaccharide (LPS). The molecule binds to a variety of leucocytes, including B cells, T cells, basophils, eosinophils and monocytes. Vascular expression of VCAM-1 has been associated with a number of disease states, including rheumatoid arthritis and vasculitis. The detection of anti-neutrophil cytoplasmic antibodies (ANCA), especially to proteinase 3 (PR3), has become important in the diagnosis of Wegener's granulomatosis (WG) and related vasculitides. Recently we were able to demonstrate a direct effect of anti-PR3 antibodies on neutrophil-endothelial interactions (Blood 1993; 82:1221). Binding of anti-PR3 antibodies to their antigen translocated into the membrane of HEC leads to an enhanced adhesion of neutrophils via induction of E-selectin (Clin Exp Immunol 1993; 94:440). The aim of this study was to investigate the effect of anti-PR3 antibodies on the expression of VCAM-1. HEC were isolated from umbilical vein and cultured on microtitre plates. After preincubation with purified anti-PR3 antibody, purified control antibodies (SS-A, SS-B, RNP) (IgG and F(ab')2 fragments) or different cytokines (controls), VCAM-1 was detected on the surface of unfixed HEC by cyto-ELISA and polymerase chain reaction analysis. Incubation of HEC with anti-PR3 antibodies led to a marked increase of endothelial VCAM-1 expression with a peak after 8 h. Incubation with TNF-alpha also led to maximal VCAM-1 expression after 4-6 h (control). Increased adhesion of T lymphocytes to HEC after binding of anti-PR3 antibodies to their antigen could be confirmed by performing adherence assays. This effect could be inhibited by antibodies to VLA-4. In conclusion, we have been able to show that cytokine-like effects of anti-PR3 antibodies on HEC are not limited to induction of neutrophil adhesion. Anti-PR3 antibodies may thus contribute to the regulation of T lymphocyte migration from the blood by HEC in ANCA-related vasculitides.

MeSH terms

  • Antibodies / immunology
  • Antibodies / pharmacology*
  • Base Sequence
  • Cell Adhesion
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / immunology*
  • Humans
  • Molecular Sequence Data
  • Myeloblastin
  • RNA, Messenger / biosynthesis
  • Serine Endopeptidases / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*
  • Vascular Cell Adhesion Molecule-1 / immunology


  • Antibodies
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1
  • Serine Endopeptidases
  • Myeloblastin