title: Regulation of tumor necrosis factor-alpha receptors on macrophages: differences between primary macrophages and transformed macrophage cell lines.
abstract: Macrophages are a pivotal cell in the production of a variety of cytokines. In addition, macrophages express receptors on their surface which allows them to act as target cells for cytokines. The regulation of both cytokine production and cytokine receptor expression in macrophages may play a key role in modulating the processes of inflammation, injury, and repair. In this report we have studied the regulation of macrophage receptors for tumor necrosis factor-alpha (TNF alpha) on rat bone marrow-derived macrophages, rat alveolar macrophages, human monocyte-derived macrophages, and the human monocyte-like cell line, U937, by a variety of immunomodulatory and inflammatory agents. U937 cells and rat and human macrophages bound TNF alpha in a saturable process, with an affinity in each cell type of approximately 1 nM. Following incubation with phorbol myristate acetate for 60 min, TNF alpha binding to all cells was decreased. Interleukin-1 treatment increased TNF alpha binding to human and rat macrophages. Interferon-gamma treatment decreased receptor activity in both human and rat macrophages, but increased TNF alpha binding to U937 cells. Treatment of human and rat macrophages with endotoxin resulted in a rapid loss of TNF alpha binding, while endotoxin treatment increased receptor expression in U937 cells. In all cases, receptor regulation was the result of a change in receptor number. Finally, following intraperitoneal injection of endotoxin, TNF alpha receptor expression was down-regulated on alveolar lavage cells from rats.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Veteran's Affairs, Nashville, TN.
authors.forename: M B
authors.initials: MB
authors.lastname: Welborn
authors.forename: J W
authors.initials: JW
authors.lastname: Christman
authors.forename: V L
authors.initials: VL
authors.lastname: Shepherd
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014115:Toxemia / Q000139:chemically induced / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha