Distinct Expression of Adhesion Molecules on Skin Fibroblasts from Patients with Diffuse and Limited Systemic Sclerosis. A Pilot Study

FLORENZO IANNONE, MARCO MATUCCI-CERINIC, PAOLA CHIARA FRANCESCA FALAPPONE, SERENA GUIDUCCI, MARINA CINELLI, OLIVER DISTLER, and GIOVANNI LAPADULA

ABSTRACT.

Objective. Systemic sclerosis (SSc) is characterized by excessive production of collagen and other components of the extracellular matrix (ECM) by fibroblasts. The ECM receptors, integrins and CD44 (hyaluronan receptor), play a key role in the homeostasis of connective tissue and may also have a role in the pathogenesis of fibrosis. We investigated the expression of integrins and CD44 on skin fibroblasts from patients with limited and diffuse SSc.

Methods. We studied 13 patients with SSc, 8 with limited SSc, and 5 with diffuse SSc, and 8 control subjects. Fibroblasts were isolated and cultured from biopsies taken from the lesional skin of the second finger of the left hand. Cell-surface expression of ß1, ß3, a1–a6, av integrins, and CD44 was evaluated by immunofluorescence and flow cytometry analysis.

Results. Fibroblasts from limited SSc showed significantly decreased expression of a2, a3, a4 integrins, while diffuse SSc fibroblasts had significantly reduced expression of a5, av integrins, and CD44. Diffuse SSc also had significantly increased expression of a6 integrin on fibroblasts. In controls, the expression of a4 and a5 correlated positively, while in limited and diffuse SSc it did not.

Conclusion. This is the first study evaluating separately the expression of adhesion molecules on skin fibroblasts from limited and diffuse subsets of SSc. We detected a distinct pattern of expression with decrease of collagen and fibronectin receptors in limited SSc, and downregulation of fibronectin and hyaluronan receptors in diffuse SSc. These results suggest that changes of fibroblasts/ECM interactions and mechanisms underlying the pathogenesis of fibrosis in SSc may differ in the single subset of the disease. (J Rheumatol 2005;32:1893-8)

Key Indexing Terms:

SYSTEMIC SCLEROSIS
CD44
ß1 INTEGRIN
ß3 INTEGRIN
a INTEGRINS
EXTRACELLULAR MATRIX

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From the Rheumatology Unit — DIMIMP, University of Bari, Bari; SOD Internal Medicine 1 and Rheumatology, AOUC Careggi, University of Florence, Florence, Italy; and Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.

Supported by grants from the University of Bari and University of Florence.

F. Iannone, MD, PhD, Consultant in Rheumatology; P.C.F. Falappone, MD, Research Assistant in Rheumatology; G. Lapadula, MD, Full Professor of Rheumatology, Rheumatology Unit — DIMIMP, University of Bari; M. Matucci-Cerinic, MD, PhD, Full Professor of Rheumatology; S. Guiducci, MD, Research Assistant in Rheumatology; M. Cinelli, MD, Research Assistant in Rheumatology, SOD Internal Medicine 1 and Rheumatology, AOUC Careggi, University of Florence; O. Distler, MD, Consultant in Rheumatology, Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich.

Address reprint requests to Prof. G. Lapadula, Rheumatology Unit–DIMIMP, Piazza G. Cesare 11, 70124 Policlinico, Bari, Italy. E-mail: g.lapadula@reumbari.uniba.it

Accepted for publication May 9, 2005.

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