Secreted extracellular domains of macrophage scavenger receptors form elongated trimers which specifically bind crocidolite asbestos.
Macrophage scavenger receptors, which have been implicated in the development of atherosclerosis and other macrophage-mediated events, are trimeric integral membrane glycoproteins whose extracellular domains have been predicted to include alpha-helical coiled-coil, collagenous and globular structures. To elucidate further the structural and functional properties of these receptors, we generated transfected Chinese hamster ovary cells which express secreted extracellular domains of the type I and type II bovine scavenger receptors and developed a solid-phase bead-binding assay to assess their ligand-binding properties. The secreted receptors exhibited the distinctive high-affinity, broad polyanionic ligand-binding specificity and the pH dependence of binding which characterize the membrane-anchored cell-surface forms of the receptors. Both the type I and type II secreted receptors were trimeric glycoproteins comprising disulfide-linked dimers and noncovalently associated monomers. Gel filtration and glycerol-gradient centrifugation established that the type II trimers were highly elongated and did not associate into higher order oligomers at the low concentrations used in these experiments. Crocilodite asbestos, which is phagocytosed by alveolar macrophages and can cause asbestosis and mesothelioma, bound efficiently to secreted type I receptors and less well to the type II receptors. This binding was specific in that it was competed by a variety of well established scavenger receptor ligands but not by negative controls. These studies have identified a new type of insoluble scavenger receptor ligand, and have raised the possibility that scavenger receptors may play a role in mediating the physiological and pathological interactions of inspired particles with alveolar macrophages.
Resnick, D; Freedman, NJ; Xu, S; Krieger, M
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