| Unveiling the role of malondialdehyde as a driver of inflammation: A dual computational and experimental approach to assess neutrophil activation by malondialdehyde-modified human serum albumin |
| Paper ID : 1210-IGA |
| Authors |
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Riadh Ben Mansour *1, Nésrine Elloumi2, Mohamed Mohany3, Sinisa Djurasevic4, Nusrat Shafiq5, Bushra Shakoor5, Aniqa Moveed5, Héla Menif6, Hend Hachicha7, Faiza Fakhfakh8 1Molecular and Functional Genetic Laboratory, Department of Life Sciences, Faculty of Sciences of Sfax, University of Sfax, Tunisia 2Research Laboratory LR18/SP12 Auto-Immunity, Cancer and Immunogenetics, Immunology Department, Habib Bourguiba University Hospital, University of Sfax 3Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia 4University of Belgrade Faculty of Biology, Belgrade, Serbia 5Synthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad-38000, Pakistan 6University of Sfax, Faculty of Medicine of Sfax, Sfax Regional Center of Blood Transfusion (CRTS), Sfax, Tuni-sia 7Research Laboratory LR18/SP12 Auto-Immunity, Cancer and Immunogenetics, Immunology Department, Habib Bourguiba University Hospital, University of Sfax, 3029, Sfax, Tunisia 8Molecular and Functional Genetic Laboratory, Department of Life Sciences, Faculty of Sciences of Sfax, Uni-versity of Sfax, Tunisia |
| Abstract |
| Background and aim: Malondialdehyde (MDA) is a highly reactive byproduct of lipid peroxidation, known to form stable adducts with proteins, making them prime targets for immune recognition. While previous studies have demonstrated the activation of adaptive immunity and antibody production against MDA-modified proteins, their role in triggering innate immune responses remains unclear. This study investigates whether human serum albumin (HSA) modified by MDA can activate neutrophils. Materials and Methods: We employed both in silico and in vitro approaches. Computational modeling was used to examine molecular interactions between HSA and MDA, with docking validation performed via MM-GBSA to evaluate binding energy. In vitro, HSA was modified with MDA at varying concentrations, followed by characterization of the modification. Human neutrophils were then isolated and treated with the MDA-HSA complex, and their activation was assessed using fluorescence and chemiluminescence assays. Results: In silico analysis revealed that MDA stably interacts with HSA us its natural ligands, ibuprofen and warfarin. The increased hydrophobicity observed in MDA-HSA complexes suggests enhanced immunogenic potential. These findings were validated by in vitro study, where MDA-modified HSA triggered dose-dependent neutrophil activation, leading to a significant rise in intracellular and extracellular reactive oxygen species production. Conclusion: Our findings demonstrate that MDA forms stable adducts with HSA, inducing structural alterations that enhance its immunogenicity. These modifications can activate neutrophils and contribute to inflammatory responses, highlighting a potential role of MDA-modified proteins in innate immunity. |
| Keywords |
| Neutrophils, HSA, Malondialdehyde, MDA-HSA adducts, innate immunity |
| Status: Accepted |
