Elsevier

Auris Nasus Larynx

Volume 28, Issue 4, November 2001, Pages 311-314
Auris Nasus Larynx

Serum levels of soluble adhesion molecules ICAM-1, VCAM-1 and E-selectin in patients with Wegener's granulomatosis

https://doi.org/10.1016/S0385-8146(01)00097-9Get rights and content

Abstract

Objective: To examine the role of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble E-selectin (sE-selectin) in the pathogenesis of Wegener's granulomatosis (WG) and the values of measuring serum levels of these soluble adhesion molecules for monitoring disease activity during follow-up, a total of 24 serum samples from 16 patients with WG were studied. Methods: The serum concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) and cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)) of patients with WG were measured by ELISA. Results: The serum levels of sICAM-1 were significantly elevated in active WG and correlated with disease activity. At the time of relapse, a significant increase of sICAM-1 was also observed. The serum levels of TNF-α and IL-6 were also significantly elevated in active WG. Conclusion: These findings suggest that sICAM-1 plays an important role in the pathogenesis of WG and may be used as an additional parameter of disease activity.

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).

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