RT Journal Article T1 A Deletion Variant of the Aspergillus fumigatus Ribotoxin Asp f 1 Induces an Attenuated Airway InflammatoryResponse in a Mouse Model of Sensitization A1 Álvarez García, Elisa A1 Batanero Cremades, Eva A1 García Fernández, Rosa Ana A1 Villalba Díaz, María Teresa A1 Gavilanes, José G. A1 Martínez Del Pozo, Álvaro AB α-Sarcin is a natural variant of Asp f 1 produced by the nonpathogenic fungus Aspergillus giganteus. Both proteins show a sequence identity of 87% and almost identical 3-dimensional structures. α-Sarcin Δ(7-22) is a deletion mutant that displays reduced immunoglobulin (Ig) E reactivity and is much less cytotoxic than wild-type proteins against human transformed cells.Objective: A murine model of sensitization to Asp f 1 was established to test the response elicited by this α-sarcin Δ(7-22) deletion mutant.Methods: BALB/c mice were treated intraperitoneally with different mixtures of recombinant wild-type Asp f 1 and/or a suspension of acommercially available A fumigatus standard extract. Mice were then intranasally challenged with Asp f 1 or α-sarcin Δ(7-22). Sera werecollected for subsequent measurement of Ig levels and histological analysis of the nostrils and lungs.Results: Sensitization to Asp f 1 was successful only when the purifi ed protein was fi rst administered together with the A fumigatus suspension.The model was characterized by elevated levels of total IgE in serum and histological lesions in the lungs and nostrils. These symptomswere less severe when the deletion variant was the protein administered, thus confi rming in vivo its lower toxic character.Conclusions: An easily reproducible mouse model of A fumigatus Asp f 1 sensitization was established. This model revealed α-sarcin Δ (7-22) to be a potential candidate for immunotherapy. PB Esmon Publicidad YR 2010 FD 2010-03 LK https://hdl.handle.net/20.500.14352/41754 UL https://hdl.handle.net/20.500.14352/41754 LA eng NO Ministerio de Educación y Ciencia de España DS Docta Complutense RD 6 oct 2024