Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor.

The mannose receptor is a single poly- peptide transmembrane glycoprotein expressed on the surface of macrophages that binds and internal- izes soluble and particulate ligands. Physiological ligands for this receptor are pathogens, such as mycobacteria, and extracellular acid hydrolases and peroxidases. Expression of the mannose recep- tor is tightly linked to the functional state of the macrophage: the receptor appears during differen- tiation, is increased by macrophage deactivating agents, and is reduced in the presence of macro- phage activating agents. Studies of the mechanisms underlying these regulatory processes have been hampered by the lack of a stable cell line that expresses a functional and appropriately regulated mannose receptor. In this study we describe expres- sion and modulation of the mannose receptor by the rat alveolar cell line NR8383. Similar amounts of the mannose receptor ligand horseradish peroxi- dase were internalized by both NR8383 cells and alveolar macrophages. In addition, NR8383 cells expressed immunoreactive mannose receptor pro- tein and mannose receptor mRNA as detected by Northern analysis. Regulation studies showed that mannose receptor expression was regulated at the levels of activity, protein, and mRNA in NR8383 cells similarly to regulation in primary rat macro- phages. In addition, NR8383 cells could be success- fully transfected with a luciferase reporter gene, providing the transfectable, mannose receptor- positive macrophage cell line. These results sup- port the hypothesis that NR8383 cells potentially represent the best current macrophage cell line for studying various aspects of macrophage function, and are particularly critical in studies of regulation of the mannose receptor, a key receptor in host defense and immune regulation. J. Leukoc. Biol. 64: 345-350; 1998.