Modulation by alpha-2 macroglobulin of human lymphocyte proliferation in response to mitogens and antigen.

The effect was studied of purified alpha-2 macroglobulin (a potent and polyvalent protease inhibitor) on normal human lymphocytes stimulated by phytohaemagglutinin, pokeweed mitogen, or by purified protein derivative as an antigen. At physiological concentration alpha 2 M has been found to inhibit mitogenic as well as antigenic stimulation. However at lower dilutions alpha 2 M acts in synergy either with the mitogen or with the antigen. At these dilutions thymidine incorporation is enhanced. alpha 2 M has no toxic or mitogenic effect on normal human lymphocytes. These data might indicate that two proteases may play a role in the proliferation of normal human lymphocytes.