Interactions of alpha1-acid glycoprotein with the immune system. I. Purification and effects upon lymphocyte responsiveness

Abstract

Alpha1-acid glycoprotein (AAG) is a constituent of normal serum which is elevated in concentration in the acute phase of inflammation; its physical and chemical properties have been defined but its biological function is uncertain. In the present study, the effect of AAG on the proliferative response of lymphocytes to several different stimuli was determined. For this purpose AAG was prepared by precipitation of human ascites fluid with sulphosalicylic acid and passage of the supernate through SP-Sephadex; the eluted protein migrated as a single band during immunoelectrophoresis, polyacrylamide gel electrophoresis and chromatography on Bio-Gel-A-1-5 m in 6 M guanidine HCl. This AAG was found to markedly inhibit the proliferative response of human peripheral blood lymphocytes to PHA; it also inhibited blastogenesis induced by Con A and PWM, but to a lesser extent. AAG was not cytotoxic to lymphocytes, and its inhibitory effects were reversed at higher mitogen concentrations. Lymphocytes preincubated with AAG remained less reactive to PHA indicating that, although AAG appeared to react with PHA, its effect was directed predominantly to the cell. Further, AAG markedly inhibited the mixed lymphocyte response, and this effect was directed to the responder cells. Thus, AAG is another acute phase reactant with the ability to modulate lymphocyte responsiveness.