NOVAL HUMAN MACROPHAGE RECEPTOR

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We have used the selective ligand CGP 42112 to modulate the novel macrophage-microglial receptor described by our group in human monocytes/macrophages and in lesions of the rat brain. We found that CGP 42112 antagonizes the macrophage stimulation produced by lipopolysacharide, inhibiting the cytokine and metalloprotein ase-g production by human macrophages. These results may suggest that CGP 42112 and related compounds can have anti-immune, anti-inflammatory properties. We have also showed that CGP 42 112 binding sites are expressed in the adventitia of balloon-catheterized arteries, suggesting a role for these receptors in the inflammatory reaction to arterial injury. In the rat brain, physical and chemical lesions result in expression of CGP 42112 receptors, and this is associated with neuronal death, both at the site of the lesion and distal to the lesion, reflecting degeneration of projecting neuronal terminals. We suggest a role for CGP 42112 receptors in the mechanisms of neuronal injury and repair. We continue our efforts to clone the novel macrophage/microglia receptor from a cDNA library from human monocytes and rat spleen.