Monocyte CD64 or CD89 targeting by surfactant protein D/anti-Fc receptor mediates bacterial uptake.
We recently showed that a chimeric protein, consisting of a recombinant fragment of human surfactant protein D (rfSP-D) coupled to a Fab' fragment directed against the human Fcalpha receptor (CD89), effectively targets pathogens recognized by SP-D to human neutrophils. The present study evaluates the effectiveness of chimeric rfSP-D/anti-Fc receptor proteins targeting Escherichia coli to CD89 or to the Fcgamma receptor I (CD64) on monocytes. Both chimeric rfSP-D/anti-Fc receptor proteins increased internalization of E. coli by the human promonocytic cell line U937, but only after induction of monocytic differentiation, despite the fact that the expression levels of CD64 and CD89 on undifferentiated cells were at least as high as on differentiated cells. The two chimeric rfSP-D/anti-Fc receptor proteins did not enhance each other's effect on E. coli uptake. Targeting to differentiated U937 cells was inhibited by blocking the interaction either between the rfSP-D part of the chimeric molecule and E. coli, or between the anti-Fc receptor Fab' fragment and the Fc receptor on the U937 cell. In conclusion, both CD64 and CD89 on U937 cells prove to be suitable for targeting by rfSP-D/anti-Fc receptor proteins. However, in addition to mere Fc receptor expression, effective targeting requires monocytic differentiation.
Department of Biochemistry and Cell Biology, Graduate School of Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Paul J
PJ
Tacken
Joseph J
JJ
Batenburg
D018033:Antibodies, Bispecific / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002117:Calcitriol / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D053773:Transforming Growth Factor beta1; D020298:U937 Cells
D018033:Antibodies, Bispecific; D015703:Antigens, CD; C036832:Fc(alpha) receptor; D037663:Pulmonary Surfactant-Associated Protein D; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002117:Calcitriol