title: The Urokinase/Urokinase Receptor System in Mast Cells: Effects of its Functional Interaction with fMLF Receptors.
abstract: Mast cell and basophils express the high affinity receptor for IgE (FcɛRI) and are primary effector cells of allergic disorders. The urokinase (uPA)-mediated plasminogen activation system is involved in physiological and pathological events based on cell migration and tissue remodelling, such as inflammation, wound healing, angiogenesis and metastasis. uPA is a serine protease that binds uPAR, a high affinity glycosyl-phosphatidyl-inositol (GPI)-anchored receptor. uPAR focuses uPA activity at the cell surface and activates intracellular signaling through lateral interactions with integrins, receptor tyrosine kinases and the G-protein-coupled family of fMLF chemotaxis receptors (FPRs). We investigated the expression of the uPA-uPAR system and its functional interaction with FPRs in human mast cells (MCs). Differently from basophils, MCs produced uPA that was able to induce their chemotaxis. Indeed, MCs also expressed uPAR, both in the intact and in a cleaved form (DII-DIII-uPAR) that can expose, at the N-terminus, the SRSRY sequence, able to interact with FPRs and to mediate cell chemotaxis. MCs also expressed mRNAs for FPRs that were functionally active; indeed, uPA and a soluble peptide (uPAR84-95), containing the SRSRY chemotactic sequence of uPAR and able to interact with FPRs, were able to induce MCs chemotaxis. Thus, uPA is a potent chemoattractant for MCs acting through the exposure of the chemotactic epitope of uPAR, that is an endogenous ligand for FPRs. The same mechanism could be involved in VEGF-A secretion by human MCs, also induced by uPA and uPAR84-95stimulation.
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Francesca Wanda
authors.initials: FW
authors.lastname: Rossi
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Nella
authors.initials: N
authors.lastname: Prevete
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Felice
authors.initials: F
authors.lastname: Rivellese
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Napolitano
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Montuori
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Postiglione
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Baronissi, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Selleri
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Amato
authors.initials: A
authors.lastname: de Paulis
keywords: FPRs; Mast Cells; VEGF-A; uPA/uPAR