The effects of electrophoretically 'slow' and 'fast' α-2 macroglobulin on mixed lymphocyte cultures

It has been determined that α-2 macroglobulin (α2M) is more suppressive of a mixed lymphocyte response (MLR) when complexed with proteinase than in its 'native' state. Other α2M preparations showed a moderate level of MLR suppression, but it is unlikely that this is a result of interaction with cellular proteinases. A panel of other proteinase inhibitors (α₁PI, SBTI, BPTI, TLCK) did not suppress the MLR to the same extent as α2M either when bound with or free from trypsin. A dose-responsive pattern of MLR suppression similar to that observed with purified proteinase-complexed α2M was seen with serum containing proteinase-complexed α2M. The population of cells that apparently conveys the suppressive property is the adherent cells (putative monocytes), which can reduce the MLR almost as well as unfractionated cells when exposed to α2M. Most of these properties of α2M were demonstrable in 'serumless' medium with qualitative similarity to the MLR obtained in cultures performed with conventional serum supplemented medium. It was found that α2M-trypsin complexes must be presented at or near culture initiation and remain in contact with the cells for a minimum of approximately 4 hr to have its optimum effect.