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Presenter: Fawad Shahab Hussain

Faculty Sponsor: Igor Kaltashov

School: UMass Amherst

Research Area: Chemistry and Materials Science

Session: Poster Session 4, 2:15 PM - 3:00 PM, Auditorium, A30

ABSTRACT

Neutrophil extracellular traps (NETs) are web-like structures composed primarily of decondensed chromatin, histones, and proteins that are released by neutrophils in response to inflammation or infectious stimuli. While NET formation plays a protective role in defending the host, a dysregulation of NETosis or overactivation can cause worsened inflammation and tissue injury or thrombosis. Lactoferrin, a highly positive glycoprotein, is abundant in neutrophil cells, and has shown to be an important regulator of NET biology due to its antimicrobial and nucleic acid-binding properties. In the context of NETs, lactoferrin can interact with several negatively charged ligands, including DNA, polyphosphate, heparin, and polysialic acid, which may affect NET structure and stability, especially in relation to downstream inflammatory and coagulatory pathways. Despite this, the specific molecular details of these non-covalent interactions, such as stoichiometry and binding affinity, remain relatively unexplored. This literature review aims to summarize current research on NET composition and function, the role of lactoferrin, activity of relevant protein-binding ligands, and the overall impact on health with a focus on immunothrombosis. There is also a focus on analytical approaches such as native mass spectrometry and size-exclusion chromatography as powerful techniques for characterizing protein-ligand complexes under close-to-physiological conditions. Such an understanding of lactoferrin and its interactions with various ligands in the context of NETs can provide a foundation for the development of therapeutic strategies that can target the regulation of inflammation and thrombosis.