抗核醣核蛋白及抗史密斯自體抗體藉減少細胞膠氨基硫抑制單核白血球增殖

Anti-ribonucleoprotein (Anti-RNP) and Anti-Smith (Anti-Sm) IgG Antibodies Penetrate into Mononuclear Cells and Impair Cell Proliferation by Decreasing Intracellular Glutathione Level

抗核醣核蛋白及抗史密斯自體抗體在每毫升200微毫克的濃度下會抑制植物血球凝集素對人類單核白血球的增殖作用，同時溶解態的細胞蛋白產物如sIL-2R, sCD4, sCD8的濃度也會減少，但卻不會影響第二介白質接受器的表現及細胞膜電位的變化，這些細胞的增殖抑制作用是經由自體抗體穿透進入細胞內作用而不是由於造成細胞的死亡，同時這種穿透作用與細胞的抗體(IgG Fc)接受器無關。進一步，我們發現這些自體抗體可在細胞活化的早期顯著地抑制膠氨基硫的產生，總結我們的發現，抗核醣核蛋白及抗史密斯自體抗體可經由穿透進入單核白血球抑制膠氧基硫的產生，並進而抑制細胞的增殖。

Anti-ribonucleoproptein (anti-RNP) and anti-Smith (anti-Sm) IgG antibodies at a concentration of 200 μg/ml inhibited 3H-thymidine incorporation of phytohemagglutinin (PHA)-stimulated normal human mononuclear cells (MNC). The concentration of soluble form of IL-2 receptor (sIL-2R), CD4 (sCD4) and CD8 (sCD8) were also decreased in the culture supernatant of PHA-stimulated MNC by these autoantibodies, However, the IL-2R expression and membrane potential of PHA-stimulated MNC were not changed by the antibodies. (The proliferation- inhibiting effect of anti-RNP and anti-Sm antibodies was caused by the penetration of these molecules into cells but did not due to cell death. Both T and B lymphocytes were penetrated by autoantibodies either in the presence or absence of PHA-stimulation.) This penetration did not depend on the IgG Fc receptor on the cells because pre-incubation of heat-aggregated human IgG with MNC did not prevent the intracytoplasmic penetration of these antibodies, Furthermore, we measured the intracellular glutathione level (GSH) in PHA-stimulated MNC after incubating with both antibodies, We found GSH level in these cells were markedly suppressed by the anti-bodies in the early stage of cell activation, These results suggest that both anti-RNP and anti-Sm IgG antibodies penetrate into MNC, suppress intracellular GSH level and lead to impairment of cell proliferation.