High-affinity pan-specific monoclonal antibodies that target cysteinyl leukotrienes and show efficacy in an acute model of colitis.

ABSTRACT: Cysteinyl leukotrienes (CysLTs) are a small family of biological signaling lipids produced by active leukocytes that contribute to diverse inflammatory disease states as a consequence of their engagement with dedicated G protein-coupled receptors. Immunization of mice with a CysLT-modified hapten carrier protein yielded novel monoclonal antibodies that display variable binding affinity to CysLTs. Solution binding assays indicated differing specificities among the antibodies tested, with antibody 10G4 displaying a preference for leukotriene C₄ (LTC₄). X-ray crystallography of a humanized 10G4 Fab fragment in complex with LTC₄ revealed that binding induces a hook-like conformation within the hydrocarbon tail of the lipid arachidonic acid moiety. Specific hydr

SUBMITTER: King AN 

PROVIDER: S-EPMC5496036 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature