CD46 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the CD46 gene is functionally disrupted in the A-549 human lung adenocarcinoma epithelial cell line. This polyclonal knockout model eliminates CD46 expression at the population level, enabling loss-of-function studies of complement regulation, viral entry, and immune modulation without clonal selection. The cells are delivered as a mixed population, reflecting the heterogeneous editing events generated by CRISPR/Cas9-mediated gene disruption, and are ideal for experimental paradigms that require a polyclonal knockout background.
The A-549 cell line, derived from the lung adenocarcinoma of a 58-year-old Caucasian male, serves as a well-characterized model for human alveolar type II pneumocytes and lung adenocarcinoma. These adherent epithelial cells exhibit features consistent with type II pneumocyte function, including surfactant production and metabolic activity, and have been extensively utilized in investigations of lung cancer biology, respiratory viral infections, and innate immune responses within the pulmonary microenvironment.
CD46 functions as a membrane cofactor protein that promotes factor I-mediated proteolytic inactivation of C3b and C4b, thereby protecting host cells from autologous complement attack. Additionally, CD46 acts as a cellular receptor for measles virus hemagglutinin and adenovirus fiber knob proteins, facilitating viral attachment and entry. The CD46 signaling network is influenced by upstream inflammatory cues such as TNF-alpha, IL-1beta, and interferon-gamma, which regulate its expression via NF-??B and STAT1. Upon engagement, CD46 modulates downstream pathways including Vav/Rac signaling, Src kinase activation, and autophagy induction, ultimately affecting T-cell activation and IL-10 secretion. CD46 also associates with tetraspanins CD9 and CD81 and integrins, linking complement defense to broader cellular adhesion and signaling complexes.
Inactivation of CD46 in A-549 cells abrogates its complement regulatory function, rendering the cells susceptible to complement-mediated lysis and increasing C3b deposition on their surface. This genetic deletion also disrupts measles virus and adenovirus entry, providing a platform to dissect viral tropism and host factors required for infection. Given the role of CD46 in autoimmune and inflammatory conditions??such as atypical hemolytic uremic syndrome, systemic lupus erythematosus, and multiple sclerosis??this knockout model is particularly relevant for exploring complement-driven pathology and immune evasion mechanisms in a lung epithelial context, where CD46 normally contributes to tissue homeostasis.
Researchers can employ CD46 Knockout A-549 Polyclonal Cells in complement-mediated lysis assays, flow cytometry for C3b deposition, and viral infectivity assays using measles virus or adenovirus vectors. The model also supports autophagy flux analysis by LC3-II monitoring and IL-10 secretion measurements, facilitating studies on immune checkpoint modulation and oncolytic virotherapy. Additional applications include high-content screening for complement pathway modulators and mechanistic exploration of CD46??s cross-talk with integrin and tetraspanin networks. For additional information about product specifications or experimental protocols, please contact Ascent Research.
