title: Effective targeting of pathogens to neutrophils via chimeric surfactant protein D/anti-CD89 protein.
abstract: 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 Fc alpha RI (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.
authors.affiliation: Department of Biochemistry and Cell Biology, Graduate School of Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tacken
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.forename: Jan G J
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: Ken B M
authors.initials: KB
authors.lastname: Reid
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Batenburg
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000378:metabolism / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody / Q000235:genetics; D002176:Candida albicans / Q000254:growth & development / Q000276:immunology; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004338:Drug Combinations; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D009980:Influenza A virus / Q000254:growth & development / Q000276:immunology; D051379:Mice; D018375:Neutrophil Activation / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000821:virology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D010587:Phagocytosis / Q000276:immunology; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology
chemical_list: D018033:Antibodies, Bispecific; D019138:Antibodies, Blocking; D015703:Antigens, CD; D002241:Carbohydrates; D004338:Drug Combinations; C036832:Fc(alpha) receptor; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D037663:Pulmonary Surfactant-Associated Protein D; D011961:Receptors, Fc; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins