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oai:docta.ucm.es:20.500.14352/944882024-08-08T00:06:38Zcom_20.500.14352_14col_20.500.14352_15

The collectin SP-A and its trimeric recombinant fragment protect alveolar epithelial cells from the cytotoxic and proinflammatory effects of human cathelicidin in vitro De Tapia Hernández, Lidia Consuelo García-Fojeda García-Valdecasas, María Belén Kronqvist, Nina Johansson, Jan Casals Carro, María Cristina 577.1 Cathelicidin LL-37 Collectin SP-A Trimeric recombinant fragment Antimicrobial activity Cytotoxicity Inflammation P2X7 channel Alveolar epithelial cells Bioquímica (Biología) 2403 Bioquímica Human cathelicidin (LL-37) is a defense peptide with antimicrobial activity against various pathogens. However, LL-37 can also trigger tissue injury by binding to host cell membranes. The cytotoxic effects of LL-37 may be especially relevant in chronic respiratory diseases characterized by increased LL-37. The aim of this study was to investigate whether the human collectin SP-A and a trimeric recombinant fragment thereof (rfhSP-A) can regulate the activities of LL-37. To this end, we studied the interaction of LL-37 with SP-A and rfhSP-A by intrinsic fluorescence, dynamic light scattering, and circular dichroism, as well as the effects of these proteins on the antimicrobial and cytotoxic activities of LL-37. Both SP-A and rfhSP-A bound LL-37 with high affinity at physiological ionic strength ( 0.45 ± 0.01 nM for SP-A and 1.22 ± 0.7 nM for rfhSP-A). Such interactions result in the reduction of LL-37-induced cell permeability and IL-8 release in human pneumocytes, mediated by P2X7 channels. Binding of LL-37 to SP-A did not modify the properties of SP-A or the antibacterial activity of LL-37 against respiratory pathogens (Pseudomonas aeruginosa, and nontypeable Haemophilus influenzae). SP-A/LL-37 complexes showed a greater ability to aggregate LPS vesicles than LL-37, which reduces endotoxin bioactivity. These results reveal the protective role of native SP-A in controlling LL-37 activities and suggest a potential therapeutic effect of rfhSP-A in reducing the cytotoxic and inflammatory actions of LL-37, without affecting its microbicidal activity against Gram-negative pathogens. Ministerio de Ciencia e Innovación (España) Comunidad de Madrid Swedish Research Council Depto. de Bioquímica y Biología Molecular Fac. de Ciencias Químicas TRUE pub 2024-01-22T16:20:47Z 2024-01-22T16:20:47Z 2022 journal article VoR https://hdl.handle.net/20.500.14352/94488 1664-3224 10.3389/fimmu.2022.994328 eng PID2021-123044OB-I00 PEJ-2020-AI/BMD-17865 Swedish Research Council 2020–02434 de Tapia L, García-Fojeda B, Kronqvist N, Johansson J and Casals C (2022) The collectin SP-A and its trimeric recombinant fragment protect alveolar epithelial cells from the cytotoxic and proinflammatory effects of human cathelicidin in vitro. Front. Immunol. 13:994328. doi: 10.3389/fimmu.2022.994328 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ open access application/pdf Frontiers