title: Fibroblast chemotaxis and prolidase activity modulation by insulin-like growth factor II and mannose 6-phosphate.
abstract: Chemotactic locomotion of fibroblasts requires extensive degradation of extracellular matrix components. The degradation is provided by a variety of proteases, including lysosomal enzymes. The process is regulated by cytokines. The present study shows that mannose 6-phosphate and insulin-like growth factor II (IGF-II) enhance fibroblast chemotaxis toward platelet-derived growth factor (PDGF). It is suggested that lysosomal enzymes (bearing mannose 6-phosphate molecules) are involved in chemotactic activity of the cells. The suggestion is supported by the observation that alpha-mannosidase and cathepsin D inhibitor-pepstatin are very potent inhibitors of fibroblast chemotaxis. Simultaneously, mannose 6-phosphate stimulates extracellular collagen degradation. The final step in collagen degradation is catalyzed by the cytosolic enzyme-prolidase. It has been found that mannose 6-phosphate stimulates also fibroblast prolidase activity with concomitant increase in lysosomal enzymes activity. The present study demonstrates that the prolidase activity in fibroblasts may reflect the chemotactic activity of the cells and suggests that the mechanism of cell locomotion may involve lysosomal enzyme targeting, probably through IGF-II/mannose 6-phosphate receptor.
authors.affiliation: Department of Medicinal Chemistry, Medical Academy of Bialystok, Poland.
authors.forename: J A
authors.initials: JA
authors.lastname: Pałka
authors.forename: E
authors.initials: E
authors.lastname: Karna
authors.forename: W
authors.initials: W
authors.lastname: Miltyk
mesh_terms: D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D004150:Dipeptidases / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008360:Mannosephosphates / Q000494:pharmacology*
chemical_list: D008360:Mannosephosphates; C027693:mannose-6-phosphate; D007335:Insulin-Like Growth Factor II; D004150:Dipeptidases; C022449:proline dipeptidase