Post-translational up-regulation of the cell surface-associated alpha component of the human type I interferon receptor during differentiation of peripheral blood monocytes: role in the biological response to type I interferon.
Human peripheral blood monocytes cultured in vitro exhibit a greater sensitivity to the antiviral effect of type I interferon (IFN) compared to freshly isolated monocytes. We evaluated the effect of macrophage differentiation on the expression of type I IFN receptors (IFN-R). Binding studies with iodinated IFN-alpha 2 and Scatchard plot analysis revealed that a single class of high-affinity receptors was present in freshly isolated monocytes. Monocyte differentiation to macrophages resulted in a three- to fourfold increase in the number of cell surface receptors with no change in their affinity. Polymerase chain reaction analysis of RNA revealed that comparable levels of mRNA for the IFN-R alpha (IFNAR1) and IFNAR2 components were expressed in freshly isolated monocytes and 7-day cultured macrophages. Likewise, the levels of IFNAR1 protein remained constant over time in culture. Immunofluorescence studies revealed that IFNAR1 was localized in intracellular compartments of freshly isolated monocytes, whereas it was predominantly detected on the cell surface in 7-day cultured macrophages. The increased expression of IFN-R on the plasma membrane of cultured macrophages may, at least in part, account for the increased antiviral effect of type I IFN in these cells. These modifications represent one of the events occurring during monocyte differentiation that may play a role in the regulation of macrophage functions.
Eantuzzi
L
L
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Eid
P
P
Malorni
W
W
Rainaldi
G
G
Gauzzi
M C
MC
Pellegrini
S
S
Belardelli
F
F
Gessani
S
S
D000293:Adolescent; D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; C508032:Ifnar1 protein, mouse; C508034:Ifnar2 protein, mouse; D007370:Interferon Type I; D008565:Membrane Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta