Schreiber S, Stenson W F, MacDermott R P, Chappel J C, Teitelbaum S L, Perkins S L
Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1991 Aug 15;147(4):1377-82.
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.
我们之前描述过，胎牛血清（FCS）中20%至40%硫酸铵可沉淀部分含有一种抑制蛋白，该蛋白可下调骨髓来源巨噬细胞上甘露糖受体的表达。我们现在确定聚集的牛IgG是主要的抑制成分。热聚集的牛IgG能够以剂量依赖的方式下调巨噬细胞甘露糖受体的表达，而不会引起配体亲和力的变化，而F(ab')2片段和未聚集的IgG均未显示出任何抑制作用。通过蛋白G亲和层析从热灭活的FCS中去除IgG可完全消除抑制活性。此外，从蛋白G层析柱重新加入Ig洗脱液可按剂量依赖的方式恢复抑制作用。巨噬细胞能够清除外源性添加的聚集牛IgG，因此与含有聚集IgG的假条件培养基相比，巨噬细胞条件培养基中的抑制活性丧失。这些结果表明，聚集的IgG通过与Fc-γR相互作用激活巨噬细胞来下调甘露糖受体的表达。
