Aggregated bovine IgG inhibits mannose receptor expression of murine bone marrow-derived macrophages via activation.
We previously described the presence of an inhibitory protein contained in the 20 to 40% (NH4)2SO4 precipitable fraction of FCS that down-regulates expression of mannose receptors on bone marrow-derived macrophages. We now identify aggregated bovine IgG as the main inhibitory component. Heat-aggregated bovine IgG was capable of down-regulating expression of the macrophage mannose receptor in a dose-dependent manner without inducing changes in ligand affinity whereas neither F(ab')2 fragments nor nonaggregated IgG displayed any inhibitory effect. Depleting of IgG from heat inactivated FCS by protein G affinity chromatography completely removes the inhibitory activity. Moreover, readdition of the Ig eluate from the protein G chromatography column restored inhibition in a dose-dependent manner. Macrophages were able to clear exogenously added aggregated bovine IgG, thus leading to loss of inhibitory activity in macrophage-conditioned media as compared to sham-conditioned media containing aggregated IgG. These results indicate that aggregated IgG down-regulates mannose receptor expression by macrophage activation via interaction with Fc-gamma R.
Schreiber
S
S
Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110.
Stenson
W F
WF
MacDermott
R P
RP
Chappel
J C
JC
Teitelbaum
S L
SL
Perkins
S L
SL
D000818:Animals; D001854:Bone Marrow Cells; D002417:Cattle; D015536:Down-Regulation; D007074:Immunoglobulin G / Q000502:physiology*; D037181:Lectins, C-Type; D008262:Macrophage Activation; D008264:Macrophages / Q000737:chemistry*; D008297:Male; D008358:Mannose / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000032:analysis*
D007074:Immunoglobulin G; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C044411:polymeric IgG; D008358:Mannose