Bernhard C. Adelmann-Grill

Collagenase gene expression in fibroblasts is regulated by a three-dimensional contact with collagen

Collagenase activity in fibroblasts is regulated by cytokines and the interaction with the extracellular matrix. In this study we demonstrate that fibroblasts cultured within a three‐dimensional collagen gel show a strong induction of collagenase gene expression. In addition to increased de novo synthesis most of the secreted enzyme was found to be activated leading to a high collagenolytic activity and complete degradation of collagen matrices after removal of fetal calf serum. Collagen I gene expression was found to be reduced under these conditions. These data suggest a specific modulation of cellular metabolism in response to contact with a three‐dimensional collagenous matrix resulting in the divergent regulation of collagen and collagenase.

Independence of Reciprocal Attachment Sites on Denatured Collagen and Fibronectin from Antigenic Sites, and Binding of Gelatin-based Plasma Substitutes to Plasma Fibronectin

Fibronectin and denatured collagen possess attachment sites for each other and, in addition, antigenic sites reacting with the respective antibodies. Using an enzyme linked immunosorbent assay it was shown that attachment sites and antigenic sites on fibronectin and on collagen reacted independently of each other. Gelatin-based plasma substitutes blocked the binding of fibronectin to denatured collagen thus showing that attachment sites for fibronectin are preserved in the gelatin preparations used for manufacturing these plasma substitutes. Antigenic sites, in contrast, were destroyed during the manufacturing process as shown with antibodies to denatured collagen raised in guinea-pigs. It is concluded that complex formation of gelatin-based plasma substitutes with plasma fibronectin may occur upon infusion of such plasma substitutes but that formation of antigen/antibody complexes in vivo is unlikely.

Pathogenetic and Clinical Significance of Fibroblast Activation in Scleroderma Lung Disease

Fibrosing alveolitis (FA) is a major and often fatal complication of systemic sclerosis (SSC). The critical role of fibroblasts in the pathogenesis of FA has long been recognized. Characterization of fibroblast activation in the lungs may improve our understanding and the management of this disease. We analyzed bronchoalveolar lavage (BAL) fluid samples from 9 healthy controls and 43 patients with FA caused by lung involvement form SSC. The chemoattractant activity (CAA) of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden chambers. In addition, procollagen III peptide was measured in BAL fluid as a marker of collagen synthesis. CAA (expressed as percentage of the chemoattractant effect of 0.25 ng/ml platelet-derived growth factor; PDGF) was elevated in the SSC patients compared with that of the controls (control: 12.6 +/- 4.0%; SSC: 68.8 +/- 15.2%; p < 0.01). A positive correlation was found between BAL total cell count and CAA (r = 0.60, p < 0.01). An inverse correlation existed between CAA and total lung capacity (r = -0.55, p < 0.05). The patients were followed up for 13.3 +/- 1.4 months (mean +/- SEM). Twenty-seven patients received immunosuppressive therapy, whereas 16 refused therapy. The patients were assigned to two groups according to their CAA being lower or higher than 36% of the PDGF response (= mean value of the controls + 2 SD).

EICOS: a European Initiative for Communicators of Science

EICOS offers European science journalists from the print and broadcast media the opportunity to gain first-hand experience of working in a scientific laboratory. In 1992 EICOS obtained support and funds from major agencies, and in the Spring of 1993 twelve of the 58 applicants were accepted as EICOS Fellows. They worked during April-May 1993 at the Max Planck Institutes (MPI) for Biochemistry and for Psychiatry near Munich, Germany, at first on a one-week programme of laboratory exercises, demonstrations and lectures. Those Fellows staying for a longer period then participated in the daily life of the host laboratories. They also gave lectures to the MPI scientists on the problems of reporting science to the public. First evaluations of the experience by the Fellows and their laboratory hosts were generally positive, and plans for an expansion and reinforcement of the programme are now being considered.