Cross-linking of both Fc gamma RI and Fc gamma RII induces secretion of tumor necrosis factor by human monocytes, requiring high affinity Fc-Fc gamma R interactions. Functional activation of Fc gamma RII by treatment with proteases or neuraminidase

Debets, J.M.; Van de Winkel, J.G.; Ceuppens, J.L.; Dieteren, I.E.; Buurman, W.A.

Journal of Immunology 144(4): 1304-1310

1990


ISSN/ISBN: 0022-1767
PMID: 2137489
Document Number: 355495
Cross-linking of Fc.gamma.R on human monocytes with human IgG has been shown to induce secretion of the inflammatory and immunoregulatory cytokine TNF. In the present study we examined the role of both constitutively expressed monocyte Fc.gamma.R, the 72-kDa high affinity Fc.gamma.R (Fc.gamma.RI), and the 40-kDa low affinity receptor (Fc.gamma.RII), in the induction of TNF secretion. On the basis of preferential binding of the Fc moiety of murine mAb of different isotype, Fc.gamma.RI and Fc.gamma.RII were selectively cross-linked by using either solid-phase murine (m)IgG2a, or solid-phase mIg1, respectively. On freshly isolated, untreated monocytes only cross-linking of Fc.gamma.RI with solid-phase mIgG2a induced TNF secretion. The interaction between Fc.gamma.RII and mIgG1 could be enhanced by treatment of monocytes with proteases or with the desialylating enzyme neuraminidase. After treatment of monocytes with these enzymes, TNF secretion was effectively induced by solid-phase mIgG1, apparently through cross-linking of Fc.gamma.RII. However, mIgG1-induced TNF secretion differed between protease-treated monocytes from high responder individuals and monocytes from low responder individuals, TNF secretion being considerably less in the latter population. Protease-treated monocytes and mononuclear cells from individuals with an inherited defect in cell membrane expression of Fc.gamma.RI were induced to secrete TNF by soid-phase human IgG, confirming the capacity of Fc.gamma.RII to induce TNF secretion. It was not possible to induce TNF secretion by cross-linking Fc.gamma.RI or Fc.gamma.RII with anti-Fc.gamma.R mAb and soluble or solid-phase anti-mIgG, indication that high affinity Fc-Fc.gamma.R interactions are necessary to induce release of this cytokine.

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