STRUCTURES AND HIGH AND LOW-AFFINITY LIGAND-BINDING PROPERTIES OF MURINE TYPE-I AND TYPE-II MACROPHAGE SCAVENGER RECEPTORS

Macrophage scavenger receptors have been implicated in various macrophage-associated processes, including atherosclerosis and clearance of bacterial endotoxin. They bind to a wide variety of polyanionic ligands and display complex binding characteristics. cDNAs from the murine macrophage-like cell line P388D1 encoding the full-length type IN and type II murine' scavenger receptors were cloned, sequenced, and ''pressed in Chinese hamster ovary cells. A fragment of the corresponding murine genomic DNA was also cloned, partially sequenced, and the positions of the cloned intron/exon boundaries were determined. Comparisons of the murine scavenger receptors' sequences with the bovine, rabbit, and human sequences were used to refine a multidomain model of these trimeric, fibrous, membrane receptors. Metabolic labeling/immunoprecipitation experiments showed that most of the macrophage scavenger receptor protein expressed by P388D1 cells was the N-glycosylated type II receptor; only small amounts of type IN receptor were detected. Analysis of the binding properties of the receptors provided evidence that such differential expression of the type IN and type II forms may have functional significance. There were substantial receptor-type (I vs. II), as well as receptor-species (bovine vs. murine), differences in the inhibition of IN-125-labeled AcLDL (acetylated low density lipoprotein) binding by ReLPS, a form of bacterial endotoxin. These differences arose, in part, because these receptors exhibited both high (K(d1)(4-degrees-C) = 0.05-0.2 mug protein/ml) and low (K(d2)(4-degreesC) = 2.5-12.8 mug protein/ml) affinity binding of I-125-labeled AcLDL. The ability of ReLPS (1 mg/ml) to inhibit either or both of these two classes of binding interactions varied depending on the species and type of receptor.