Monocyte activation by tumour cells: a role for carbohydrate structures associated with CD2.
Monocytes/macrophages can kill tumour cells and mediate tumour-destructive host responses e.g. by releasing tumour necrosis factor-alpha (TNF-alpha). The underlying mechanisms of tumour cell recognition, however, are not clear. Previous work in our laboratory suggested that carbohydrate moieties associated with the T cell adhesion molecule CD2 of Jurkat cells induce TNF-alpha secretion by human monocytes. In this study we present data indicating that the stimulatory capacity for TNF-alpha secretion is confined to carbohydrate moieties of tumour cell CD2. Irradiated resting peripheral T cells did not display stimulatory activity in contrast to irradiated Jurkat cells although surface expression of CD2 was similar. Activated T cells, however, induced TNF-alpha production by monocytes via a CD2-independent mechanism. Only affinity purified CD2 prepared from Jurkat cells but not from non-transformed T cells activated monocytes to secrete TNF-alpha. This activation process was blocked by anti-CD2 antibodies. Neuraminidase and PNGaseF treatment of isolated CD2 inhibited the stimulatory capacity whereas pronase treatment did not. These data suggest that carbohydrate moieties containing sialic acid mediate stimulation of monocytes. Taken together, these results indicate a role for glycosylation patterns typical of tumour cells in the recognition process of tumour cells by monocytes/macrophages.
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Institut für Pathologie/Tumorimmunologie, Universitätsklinikum Regensburg, Germany.
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D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D018801:CD2 Antigens / Q000737:chemistry / Q000276:immunology*; D002241:Carbohydrates / Q000276:immunology*; D002455:Cell Division; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D018801:CD2 Antigens; D002241:Carbohydrates; D014409:Tumor Necrosis Factor-alpha