Macrophage membrane glycoprotein binding of Griffonia simplicifolia I‐B4 induces TNF‐alpha production and a tumoricidal response

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Abstract
Thioglycollate‐elicited macrophages (mϕ), upon binding the lectin Griffonia simplicifolia IB4 (GSIB4) 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 GSIB4 used and the time in contact with the cells. At 40 μg/ml GSIB4, 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 GSIB4 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 GSIB4 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 (IP3) levels were examined, the results showed that the concentration of cAMP was unchanged despite the fact that IP3 levels were significantly enhanced upon mϕ‐GSIB4 binding. Collectively, the data show that GSIB4 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 GSIB4 is presented to the mϕ relative to the IFN/LPS treatment.