α₁-Antitrypsin is an effector of immunological stasis

Abstract

SEVERAL proteins in normal serum can serve as suppressors or enhancers of the immune response. Recently an α-globulin-rich fraction of Cohn fraction IV, designated IRA (immuneregulatory α-globulin), has been implicated in suppressing the in vitro antibody response of mouse spleen cells to sheep red cells without cytotoxicity¹. Studies by Chase² also indicate that α₂-macroglobulin, one of the protease inhibitors present in normal serum, limits the human lymphocyte response to phytohaemagglutinin, and concanavalin A as measured by ³H-thymidine incorporation. A similar role for α₁-antitrypsin (α₁-AT), the major protease inhibitor in normal serum, can be proposed for involvement in the regulation of the immune response. Proteases have been found on both the surface and in the medium of cultured cells³; they have also been implicated in altering the electrophoretic mobility⁴, in vivo migration⁵ and blast transformation⁶ of lymphocytes. The physiological function of α₁-AT in the serum is unknown. It is not clear why there is an increase of this protease inhibitor in certain physiological and pathological conditions⁷. Results presented here suggest that α₁-AT has an immunoregulatory role, by suppressing the in vivo and in vitro immune response of mouse spleen cells against sheep red cells (SRBC).