Surfactant protein D/anti-Fc receptor bifunctional proteins as a tool to enhance host defence.
BACKGROUND
Drug-resistant pathogens are an increasing threat, particularly for hospitalised patients. In search of a new approach in pathogen targeting, we developed bifunctional proteins that combine broad spectrum pathogen recognition with efficient targeting to phagocytes. Pathogen recognition is provided by a recombinant fragment of surfactant protein D (rfSP-D) while targeting to phagocytic cells is accomplished by coupling rfSP-D to F(ab') fragments directed against Fcalpha receptor I (FcalphaRI) or Fcgamma receptor I (FcgammaRI). FcalphaRI and FcgammaRI are expressed on myeloid cells, and induce rapid internalisation of particles after crosslinking.


OBJECTIVE
In this review we discuss the roles of SP-D and Fc receptors in host defence as a rationale for rfSP-D/anti-FcR bifunctional proteins. Furthermore we summarise the available data on rfSP-D/anti-FcR proteins as well as opportunities and considerations for future use of such bifunctional proteins.


CONCLUSIONS
rfSP-D/anti-FcR bifunctional proteins could be of great value for the treatment of a variety of infectious diseases. The focus in the near future should be on proof-of-principle by testing the bifunctional proteins in different mouse models of infectious disease.
Breij
Esther C W
EC
Utrecht University, Department of Biochemistry and Cell Biology, Veterinary Sciences Faculty, Yalelaan 2, 3584 CM Utrecht, The Netherlands. e.c.w.breij@uu.nl
Batenburg
Joseph J
JJ
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D003141:Communicable Diseases / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007113:Immunity, Innate; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D010586:Phagocytes / Q000276:immunology; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology / Q000627:therapeutic use*; D011961:Receptors, Fc / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007140:Immunoglobulin Fab Fragments; D037663:Pulmonary Surfactant-Associated Protein D; D011961:Receptors, Fc; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins