Immunomodulation by α₂‐macroglobulin and α₂‐macroglobulin‐proteinase complexes: the effect on the human T lymphocyte response

Abstract

Alpha 2-macroglobulin (alpha 2M), various alpha 2M-proteinase complexes and methylamine-treated alpha 2M were added to human lymphocyte cultures stimulated with the specific antigen purified protein derivative of tuberculin (PPD), pokeweed mitogen (PWM) and anti-CD3. alpha 2M-trypsin diminished all reactions in a dose-dependent way. In the PPD-induced stimulation of peripheral blood mononuclear cells, both change of configuration and remaining proteinase activity contributed to the suppressive activity. Separate exposure of adherent cells or the highly purified T lymphocytes to alpha 2M-trypsin complexes indicated that the effect was mediated through adherent cells. Addition of indomethacin did not modify the results. In the interleukin 2 (IL2)-dependent stimulation of purified T lymphocytes by anti-CD3 the effect of alpha 2M-proteinase complexes was probably due to the digestion of IL 2 through remaining proteinase activity. As alpha 2M-proteinase complexes are formed at sites of inflammation, the multiple immunomodulatory effects of alpha 2M-proteinase complexes might contribute to the dysregulation of the immune system in inflammatory diseases.

Inhibition of intracellular proteolytic processing of soluble proproteins by an engineered α2-macroglobulin containing a furin recognition sequence in the bait region

“…Analysis of the different rα # M forms by non-denaturing PAGE showed ' slow ' mobility [27] for WT\furin-rα # M, whereas FUR\ furin-rα # M migrated with a mobility intermediate between ' slow ' and trypsin-generated ' fast ' α # M (Figure 3, lanes 3 and 4). This intermediate mobility was previously observed when p-α # M was reacted with high-molecular-mass proteases such as thrombin, kallikrein and plasmin [28][29][30][31]. Treatment of FUR\furin-rα # M with trypsin increased the mobility to ' fast ' (Figure 3, lane 12).…”

Diagnostic and Predictive Value of an Immune Monitoring Program for Complications after Kidney Transplantation

“…In fact, the expression of HLA-DR antigens on the monocytes and their antigen-presenting function is inhibited in vitro after a strong phagocytosis stimulus. This effect could be reversed by scavenger of reactive oxygen species [18.19], Other products of inflammation such as prostaglandins, ob-macroglobulin-proteinase complexes and activated complement factors also exert a negative regulating func tion on the expression of HLA-DR antigens on mono cytes/macrophages [ 17,20],…”

The Emerging Role of Serratiopeptidase in Oral Surgery: Literature Update

“…It dissolves the dead tissue surrounding the injured area without harming living tissue, thereby accelerating healing. Several studies have proved that orally administered proteolytic enzymes can specifically control the inflammatory cytokines and the onset of chronic inflammation [15][16][17]. Serrapeptidase and other proteolytic enzymes are effective in controlling and modulating inflammatory processes are referred to as "adjunct therapeutic agents" [18].…”