Engineered Mannose-Binding Lectin (FcMBL) Decreases Macrophage Phagocytosis

Mannose-binding lectin (MBL) is an innate immune system opsonin that binds a large variety of pathogen-associated molecular patterns (PAMPs) on bacteria, fungi, viruses, parasites and toxins, leading to the activation of the lectin compliment pathway, coagulation, and opsonization of pathogens for phagocytosis. Due to its opsonizing abilities, MBL can be used to diagnose and treat blood-borne infections, including sepsis. We have engineered a recombinant protein (FcMBL) by fusing the Fc domain of IgG1 to the pathogen-binding domains of MBL. FcMBL preserves the capabilities of wild-type MBL to recognize and bind pathogen, while avoiding the subsequent immune responses normally produced by wild-type MBL, such as complement activation, coagulation, and inflammation. In the present study, we have differentiated THP-1 acute monocytic leukemia cells into monocyte-derived macrophages (MDM) using 12-O-tetradecanoylphorbol-13-acetate (PMA) and used these to test MBL-dependent phagocytosis. Phagocytosis levels were...