Cementoin-SLPI fusion protein binds to human monocytes and epithelial cells and shows higher biological activity than SLPI

Secretory Leukocyte Proteinase Inhibitor (SLPI) is an antiinflammatory peptide that blocks the activity of serine proteases, primarily the neutrophil elastase. In an attempt to direct the activity of SLPI on inflamed sites, a chimera consisting of the transglutaminase II substrate domain of trappin...

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Detalles Bibliográficos
Autores: Maffia, Paulo Cesar, Guerrieri, Diego, Villalonga, Ximena Soledad, Caro, Fiorella Yanina, Gómez, Sonia Alejandra, Tateosian, Nancy Liliana, Bogado, Betiana P., Sánchez, Mercedes Leonor, Ambrosi, Nella Gabriela, Chuluyan, Hector Eduardo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/87187
Acceso en línea:http://hdl.handle.net/11336/87187
Access Level:acceso abierto
Palabra clave:Cementoin?SLPI
monocyte
fusion protein
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario:Secretory Leukocyte Proteinase Inhibitor (SLPI) is an antiinflammatory peptide that blocks the activity of serine proteases, primarily the neutrophil elastase. In an attempt to direct the activity of SLPI on inflamed sites, a chimera consisting of the transglutaminase II substrate domain of trappin 2 (cementoin), and the mature SLPI protein was constructed. Cell attachment and biological activity were compared between SLPI and this chimera. By using whole cell ELISA, fluorescence microscopy and flow cytometry assays we observed that the cementoin-SLPI fusion protein (FP) but not SLPI attached to a human lung epithelial cell line and monocytes. A maximum attachment was achieved 15 min after FP was added to the cell cultures. In an elastase activity assay, we observed that FP retained its antiprotease activity and that at equimolar amount of proteins, FP was more efficient than SLPI in the inhibition. Both, FP and SLPI inhibits IL-2-induced lymphocyte proliferation, however, lower amounts of FP were required to achieve this inhibition. Furthermore, FP binds to mycobacteria and maintained the bactericidal activity observed for SLPI. Overall, these results show that this new chimera is able to attach to the cell surfaces retaining and improving some biological activities described for SLPI.