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FcR -Chain Dependent Signaling in Immature Neutrophils Is Mediated by FcRI, but Not by FcRI¹

Marielle A. Otten^*,, Jeanette H. W. Leusen^*, Esther Rudolph^*,, Joke A. van der Linden^*, Robert H. J. Beelen, Jan G. J. van de Winkel^*, and Marjolein van Egmond^2,,

^* Immunotherapy Laboratory, Department of Immunology, University Medical Center, Utrecht, The Netherlands; Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands; Genmab, Utrecht, The Netherlands; and Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands

Neutrophil-mediated tumor cell lysis is more efficiently triggered by FcRI (CD89), than by FcRI (CD64). This difference is most evident in immature neutrophils in which FcRI-mediated tumor cell lysis is absent. In this study, we show that FcR -chain-dependent functions (such as Ab-dependent cellular cytotoxicity and respiratory burst), as well as signaling (calcium mobilization and MAPK phosphorylation), were potently triggered via FcRI, but not via FcRI, in immature neutrophils. Internalization, an FcR -chain-independent function, was, however, effectively initiated via both receptors. These data suggest an impaired functional association between FcRI and the FcR -chain, which prompted us to perform coimmunoprecipitation experiments. As a weaker association was observed between FcRI and FcR -chain, compared with FcRI and FcR -chain, our data support that differences between FcRI- and FcRI-mediated functions are attributable to dissimilarities in association with the FcR -chain.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Dutch Cancer Society (UU2001-2431) and the Netherlands Organization for Scientific Research (VENI 916.36.079).

² Address correspondence and reprint requests to Dr. Marjolein van Egmond, Department of Molecular Cell Biology and Immunology, Vrije University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. E-mail address: M.vanEgmond{at}vumc.nl

³ Abbreviations used in this paper: ADCC, Ab-dependent cellular cytotoxicity; m, murine; BsAb, bispecific Ab; PO, peroxidase; P-MAPK, phosphorylated MAPK; A.U., arbitrary unit; AUC, area under the curve; NP40, Nonidet P-40; RIPA, radioimmunoprecipitation.