Serum levels of soluble adhesion molecules ICAM-1, VCAM-1 and E-selectin in patients with Wegener's granulomatosis
Introduction
The upregulation and enhanced expression of cytokine-inducible cell surface adhesion molecules on neutrophils and on normally non-adhesive vascular endothelium leads to the adherence of inflammatory cells to vessel walls, their activation and subsequent extravasation. The occurrence of adhesion molecules that are in soluble form, consequently lacking the transmembrane and intracellular domain and consisting of the extramembranous part of the molecule only, was first described for ICAM-1 and later for VCAM-1 and E-selectin [1], [2], [3], [4], [5], [6]. These soluble adhesion molecules have been found both in vitro in the supernatants of cultured cytokine-stimulated endothelial cells and in vivo in human plasma or serum. Since they retain the ability to bind their ligands, it is thought that these soluble forms of adhesion molecules play a role in regulating the immune response. They are probably shed or cleaved from the cell membrane after expression, since no evidence for secretion or production of a spliced form by the activated cells has thus far been found. Several studies have demonstrated elevated levels of sICAM-1, sVCAM-1, or sE-selectin in relation to disease activity in various acute and chronic inflammatory diseases, and some authors have advocated the use of these soluble adhesion molecules as markers for disease activity in autoimmune diseases [7], [8].
This study was performed to assess the role of the three soluble adhesion molecules in WG with respect to their importance in the pathogenesis, and as a parameter of disease activity.
Section snippets
Sera and patients
Serum samples were obtained from 16 patients with WG (10 males, six females; average age 56.5 years: 20–69 years) and from six healthy volunteers. Serum was separated from clotted samples by centrifugation and stored at −70°C until use. Serum samples obtained at the time of diagnosis were tested for levels of these soluble adhesion molecules in active WG. They received corticosteroids and cyclophosphamide as immunosuppressive combination therapy. Organ involvement was documented according to
Results
Serum levels of sICAM-1 of patients with WG were examined, and the concentration of sICAM-1 was significantly elevated in active WG compared to WG in remission and healthy controls (Fig. 1). Next, serum levels of sVCAM-1 were also measured. Although sVCAM-1 concentrations were lower in inactive WG than in active WG, the differences were not significant (Fig. 2). The serum levels of sE-selectin in all study groups were not elevated compared to healthy donors (Fig. 3). We next examined serial
Discussion
In this study, we measured the levels of soluble adhesion molecules in serum samples from patients with WG to correlate those levels with clinical disease activity. It was hoped that, given the basic role played by adhesion molecules in inflammatory reactions, the levels of soluble adhesion molecules could be used for monitoring the disease activity of WG during follow-up. Given the restricted expression of VCAM-1 and especially ICAM-1, soluble levels of these adhesion molecules might function
Acknowledgements
This study was supported by grants from the Ministry of Education, Science, Sports and Culture (Grant in Aids for Scientific Research A 12770944).
References (16)
- et al.
Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders
Lancet
(1991) - et al.
Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that bind to lymphocytes
Cell
(1989) - et al.
Circulating ICAM-1Isoforms; diagnostic prospects for inflammatory and immune disorders
Lancet
(1991) - et al.
Autoantibodies against neutrophils and monocytes; tool for diagnosis and marker of disease activity in Wegener's granulomatosis
Lancet
(1985) - et al.
The expression OF ELAM-1, ICAM-1 and VCAM-1 in experimental cutaneous inflammation; a comparison of Uvb erythema and delayed hypersensitivity
J Invest Dermatol
(1991) Adhesion receptors of the immune system
Nature
(1990)- et al.
A form of circulating ICAM-1 in human serum
J Immunol
(1991) - et al.
Expression and functional characterization of a soluble form of vascular cell adhesion molecule 1
Biochem Biophys Res Commun
(1991)