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Expression of tumor necrosis factor receptors on human monocytes and internalization of receptor bound ligand
Authors:K Imamura  D Spriggs  D Kufe
Affiliation:Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Abstract:Tumor necrosis factor (TNF) is a polypeptide produced by monocytes and macrophages. Although TNF receptors have been identified on a variety of cell types, previous studies have not determined whether these receptors also exist on monocytes. In the present work, highly purified recombinant TNF was labeled with 125I. The 125I-labeled TNF bound specifically to receptors on human monocytes and monocyte membrane preparations. A curvilinear Scatchard plot indicated the presence of TNF-binding sites with two different affinities. The results also indicate that receptor-bound TNF is rapidly internalized by monocytes and then degraded intracellularly. These findings are in concert with recent studies demonstrating that TNF immunomodulates monocyte function by an autocrine mechanism.
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