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Effective Targeting of Pathogens to Neutrophils via Chimeric Surfactant Protein D/Anti-CD89 Protein¹

Paul J. Tacken^*, Kevan L. Hartshorn, Mitchell R. White, Cees van Kooten, Jan G. J. van de Winkel, Ken B. M. Reid^¶ and Joseph J. Batenburg^2,*

^* Department of Biochemistry and Cell Biology, Graduate School of Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Department of Medicine, Boston University School of Medicine, Boston, MA 02118; Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands; Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; Genmab, Utrecht, The Netherlands; and ^¶ Medical Research Council, Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford, United Kingdom

Targeting of specific pathogens to FcRs on immune effector cells by using bispecific Abs was reported to result in effective killing of the pathogens, both in vitro and in vivo. Instead of targeting a specific pathogen to an FcR, we assessed whether a broad spectrum of pathogens can be targeted to an FcR using surfactant protein D (SP-D). SP-D is a collectin that binds a great variety of pathogens via its carbohydrate recognition domain. A recombinant trimeric fragment of SP-D (rfSP-D), consisting of the carbohydrate recognition domain and neck domain of human SP-D, was chemically cross-linked to the Fab' of an Ab directed against the human FcRI (CD89). In vitro, the chimeric rfSP-D/anti-CD89 protein enhanced uptake of Escherichia coli, Candida albicans, and influenza A virus by human neutrophils. Blocking of the interaction between rfSP-D/anti-CD89 and either the pathogen or CD89 abolished its stimulatory effect on pathogen uptake by neutrophils. In addition, rfSP-D/anti-CD89 stimulated killing of E. coli and C. albicans by neutrophils and enhanced neutrophil activation by influenza A virus. In conclusion, rfSP-D/anti-CD89 effectively targeted three structurally unrelated pathogens to neutrophils. (Col)lectin-based chimeric proteins may thus offer promise for therapy of infectious disease.

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