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Macrophage membrane glycoprotein binding of Griffonia simplicifolia I‐B4 induces TNF‐alpha production and a tumoricidal response
Author(s) -
Tabor Dale R.,
Theus S. A.,
Barnett John B.,
Jacobs Richard F.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041520309
Subject(s) - tumor necrosis factor alpha , receptor , griffonia simplicifolia , lectin , cytokine , glycoprotein , cell surface receptor , membrane glycoproteins , microbiology and biotechnology , secretion , biochemistry , chemistry , biology , immunology
Thioglycollate‐elicited macrophages (mϕ), upon binding the lectin Griffonia simplicifolia IB 4 (GSIB 4 ) at the plasma membrane, are induced to secrete several low molecular weight proteins. In this investigation, results from specific ELISA and immunoprecipitation analysis of these molecules confirmed that the cytokine, tumor necrosis factor‐α (TNF‐α), belongs to the group of elicited proteins. This specific mϕ response is directly influenced by the dose of GSIB 4 used and the time in contact with the cells. At 40 μg/ml GSIB 4 , the maximum dose of lectin used, the mϕ activity was equal to that achieved when the cells were incubated with an interferon‐γ/lipopolysaccaride (IFN/LPS) stimulus alone. Moreover, the data showed that TNF‐mediated tumoricidal activity was significantly influenced by GSIB 4 binding to the mε membrane. When the lectin was incubated alone or in sequence with IFN/LPS, this ligand‐receptor binding promoted the lysis of WEHI 164 tumor target cells. However, concurrent incubation of both IFN/LPS and GSIB 4 with mϕ significantly diminished the tumoricidal response. This suggested that one of the metabolic pathways utilized subsequent to receptor‐ligand binding was altered by these interactions. When cyclic AMP (cAMP) and inositol triphosphate (IP 3 ) levels were examined, the results showed that the concentration of cAMP was unchanged despite the fact that IP 3 levels were significantly enhanced upon mϕ‐GSIB 4 binding. Collectively, the data show that GSIB 4 binding to specific glycoproteins in the mϕ membrane induces TNF‐α production and facilitates TNF‐α dependent tumoricidal responses. It also appears that the transduction of the signal, in part, at least utilizes the phosphatidyl inositol pathway. Finally, it is noteworthy that mϕ activity is influenced by the sequence in which GSIB 4 is presented to the mϕ relative to the IFN/LPS treatment. © 1992 Wiley‐Liss, Inc.