Enhanced degradation of proteins of the basal lamina and stroma by matrix metalloproteinases from the salivary glands of Sjögren's syndrome patients: Correlation with reduced structural integrity of acini and ducts

• Published in: Arthritis and rheumatism Vol. 48; no. 9; pp. 2573 - 2584
• Main Authors: Goicovich, Eduardo, Molina, Claudio, Pérez, Paola, Aguilera, Sergio, Fernández, Juan, Olea, Nancy, Alliende, Cecilia, Leyton, Cecilia, Romo, Rafael, Leyton, Lisette, González, María‐Julieta
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-09-2003; Wiley
• Subjects: Adult; Basement Membrane - enzymology; Basement Membrane - pathology; Biological and medical sciences; Collagen Type IV - metabolism; Extracellular Matrix - enzymology; Extracellular Matrix - pathology; Humans; Laminin - metabolism; Matrix Metalloproteinases - metabolism; Medical sciences; Microscopy, Electron; Middle Aged; Salivary Ducts - enzymology; Salivary Ducts - pathology; Salivary Ducts - ultrastructure; Salivary Glands - enzymology; Salivary Glands - pathology; Salivary Glands - ultrastructure; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sjogren's Syndrome - metabolism; Sjogren's Syndrome - pathology; Substrate Specificity; Human; Immunopathology; Biochemical analysis; Enzyme; Stomatology; Pathogenesis; Labial gland; Autoimmune disease; Metalloendopeptidases; Salivary gland; Sjögren syndrome; Gelatinase B; Gelatinase A; Degradation; Peptidases; Eye disease; Enzymatic activity; Systemic disease; Hydrolases; Extracellular matrix
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.11178

Objective
To determine the effect of matrix metalloproteinase (MMP) activity from the labial salivary glands (LSGs) of Sjögren's syndrome (SS) patients on proteins of the extracellular matrix (ECM) that form the basal lamina and stroma, and to compare this effect with the structural integrity of acini and ducts as well as the functionality of the LSGs.
Methods
Gelatinase activity was determined by zymography. The digestion pattern of extracellular matrix (ECM) macromolecules was detected by gel electrophoresis and quantified by densitometry. The structural integrity of acini and ducts was evaluated by light and electron microscopy. Secretory function was evaluated by measuring unstimulated salivary flow and by scintigraphy.
Results
LSG extracts showed increased levels of proteolytic activity toward purified proteins of the basal lamina (laminin and type IV collagen) and stroma (types I and III collagen and fibronectin). Enhanced degradation was most evident for fibronectin, laminin, and type IV collagen. Analysis of the ultrastructure of the acinar and ductal basal lamina revealed abnormalities ranging from disorganization to disappearance of this ECM structure. These changes were paralleled by an important loss of microvilli on the apical surface, as well as decreased unstimulated salivary flow. Interestingly, the results were similar in LSGs from all SS patients, regardless of the proximity of infiltrating mononuclear cell foci.
Conclusion
Our observation that the proteolytic action of MMPs toward ECM macromolecules is increased in SS patients provides a rationale for understanding the dramatic changes in the structural organization observed in the basal lamina and apical surface of acini in these patients. The results provide new evidence that acinar and ductal cells from the LSGs of SS patients display a molecular potential, with increased capacity to markedly disorganize their ECM environment and, thus, damage their architecture and functionality.