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 macroph age-associated processes, including atherosclerosis and clearance of b acterial endotoxin. They bind to a wide variety of polyanionic ligands and display complex binding characteristics. cDNAs from the murine ma crophage-like cell line P388D1 encoding the full-length type IN and ty pe II murine' scavenger receptors were cloned, sequenced, and ''presse d in Chinese hamster ovary cells. A fragment of the corresponding muri ne 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 trim eric, fibrous, membrane receptors. Metabolic labeling/immunoprecipitat ion experiments showed that most of the macrophage scavenger receptor protein expressed by P388D1 cells was the N-glycosylated type II recep tor; only small amounts of type IN receptor were detected. Analysis of the binding properties of the receptors provided evidence that such d ifferential expression of the type IN and type II forms may have funct ional significance. There were substantial receptor-type (I vs. II), a s well as receptor-species (bovine vs. murine), differences in the inh ibition of IN-125-labeled AcLDL (acetylated low density lipoprotein) b inding by ReLPS, a form of bacterial endotoxin. These differences aros e, in part, because these receptors exhibited both high (K(d1)(4-degre es-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 b inding interactions varied depending on the species and type of recept or.