Onderdelen van het celoppervlak die de binding beïnvloeden van calciumoxalaat-kristallen aan niertubuli-cellen in kweek. Welke zijn dat en wat reguleert ze?
1999 - onbekend
Binding to renal tubule epithelial cells may turn harmless urine crystals into a stone nidus. Prevention of crystal attachment could therefore add to existing stone treatment, which mainly aims at the inhibition of crystal formation and growth. The mechanisms of crystal-cell binding are still poorly understood. We have used a model system, based on the renal tubule cell line MDCK-I with characteristies of renal collecting duct cells. In these cells, the crystal binding capacity depends on the stage of culture development. In contrast to renal cell lines that are representative for earlier parts of the nephron, MDCK-I cells acquire nearly complete protection from crystal binding during their organization into a functional monolayer. This seems to reflect a functional property of the nephronal origin, considering that crystal formation is expected to occur primarily in the late parts of the nephron. Epithelial injury and the subsequent wound healing process compromised protection from crystal adherence to confluent MDCK-I monolayers. We propose that crystals bind to specific sites at the cell surface that are normally absent/inaccessible, but present/accessible during epithelial development or wound healing. Identification and molecular characterization of these sites is our major airn. For that purpose we will further explore the effects on crystal binding of selective enzymatic removal (by sialidases, hyaluronidase, chondroitinase and/or trypsin) of candidate receptor molecules (e.g. glycoconjugates) from the cell surface and characterize the released (metabolically labeled) products. Also the possible role of membrane phospholipids (phosphatidylserine) in crystal attachment will be studied. Furthermore, the effects of physiologically relevant conditions, such as high oxalate and crystal concentrations, on cell surface composition and crystal binding will be examined. Finally, studies on the mechanisms that control the expression of potential crystal binding molecules at the cell surface will be initiated.