INTERACTIONS OF ALPHA1-ACID GLYCOPROTEIN WITH IMMUNE SYSTEM .1. PURIFICATION AND EFFECTS UPON LYMPHOCYTE RESPONSIVENESS

Abstract

.alpha.1-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. The effect of AAG on the proliferative response of lymphocytes to several different stimuli was determined. AAG was prepared by precipitation of human ascites fluid with sulfosalicylic 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 markedly inhibited the proliferative response of human peripheral blood lymphocytes to PHA [phytohemagglutinin]; it also inhibited blastogenesis induced by Con A [concanavalin A] and PWM [pokeweed mitogen], 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. AAG markedly inhibited the mixed lymphocyte response; this effect was directed to the responder cells. AAG is another acute phase reactant with the ability to modulate lymphocyte responsiveness.