Urokinase Plasminogen Activator, uPa Receptor, and Its Inhibitor in Vernal Keratoconjunctivitis

• Published in: Investigative ophthalmology & visual science Vol. 46; no. 4; pp. 1364 - 1370
• Main Authors: Leonardi, Andrea, Brun, Paola, Sartori, Maria Teresa, Cortivo, Roberta, DeDominicis, Chiara, Saggiorato, Graziella, Abatangelo, Giovanni, Secchi, Antonio G
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.04.2005; Association for Research in Vision and Ophtalmology
• Subjects: Adolescent; Biological and medical sciences; Cells, Cultured; Child; Child, Preschool; Conjunctiva - cytology; Conjunctivitis, Allergic - metabolism; Diseases of cornea, anterior segment and sclera; Epithelial Cells - metabolism; Female; Fibroblasts - metabolism; Humans; Immunoenzyme Techniques; Male; Medical sciences; Ophthalmology; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Urokinase Plasminogen Activator; Reverse Transcriptase Polymerase Chain Reaction; RNA - isolation & purification; RNA, Messenger - metabolism; Tears - metabolism; Tissue Plasminogen Activator - genetics; Tissue Plasminogen Activator - metabolism; Urokinase-Type Plasminogen Activator - genetics; Urokinase-Type Plasminogen Activator - metabolism; u-Plasminogen activator; Serine endopeptidases; Enzyme; Keratopathy; Conjunctiva disease; Peptidases; Eye disease; Keratoconjunctivitis; Activator; Hydrolases; Inhibitor; Ophthalmology; Plasminogen; Anterior segment disease
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.04-1196

Plasminogen activators play a role, not only in fibrinolysis but also in events such as chemotaxis, collagen degradation, and cell spreading. The serine protease urokinase (uPA) is a potent chemoattractant for leukocytes that may be involved in the pathogenesis of severe forms of allergic conjunctivitis such as vernal keratoconjunctivitis (VKC). Tear and peripheral blood samples were obtained from 20 patients with active VKC and from 19 normal subjects who formed the control group. Levels of plasminogen activity, uPA, tissue plasminogen activator (tPA), and their inhibitor, plasminogen activator inhibitor type-1 (PAI-1) were measured in tears and plasma of patients with VKC. The presence of tPA, uPA, and urokinase receptor (uPAR) in conjunctival tissues were evaluated by immunohistochemistry. uPA, uPAR, and PAI-1 expression and production were measured in conjunctival epithelial cell and fibroblast cultures treated with cytokines. Tear levels of uPA and tPA and tear plasminogen activity levels were significantly greater in patients with VKC than in control subjects. Increased staining for uPA and uPAR was found in VKC tissues compared with normal conjunctiva. Both conjunctival epithelial cells and fibroblasts demonstrated an increased expression of uPAR after exposure to IL-4 or -13, whereas uPA was highly expressed by epithelial cells exposed to IL-4. PAI-1 levels in culture medium were increased in IL-4-exposed epithelial cells compared to nonstimulated cells and were decreased in fibroblast culture. Increased expression of fibrinolytic system components and imbalance between plasminogen activators and PAI may be involved in the pathogenesis of severe allergic conjunctivitis, thus contributing to inflammatory cell migration and tissue remodeling.