Glutaminyl-peptide gamma-glutamyltransferase dependence of the uptake of trypsin-alpha-macroglobulin complexes by macrophages.

The canine alpha-macroglobulin 125I-trypsin complexes were prepared and exposed to canine alveolar macrophages. The binding of the complexes to cells was time- and dose-dependent. A rapid uptake and degradation of the bound complexes was evidenced by the finding of less than 20% cell-bound radioactivity after a 4 h incubation at 20 degrees C. The canine alveolar macrophages contain a glutaminyl-peptide gamma-glutamyltransferase which shows slightly retarded agarose gel electrophoretic mobility as compared to the respective enzymes from tissues of other species, such as guinea pig and man. Evidence is presented that the binding and degradation of trypsin alpha-macroglobulin complexes by macrophages is dependent on this gamma-glutamyltransferase. Monodansylthiacadaverine, a strong inhibitor of this enzyme, blocks the binding of trypsin-alpha-macroglobulin complexes to macrophages and (probably as a consequence of this) degradation of the complexes. Furthermore, this gamma-glutamyltransferase is a calcium-dependent enzyme and the process of binding trypsin-alpha-macroglobulin complexes to the macrophages was likewise found to be calcium-dependent.