Characteristics of the macrophage uptake of proteinase-alpha-macroglobulin complexes.

Complexes formed between labelled proteolytic enzymes (trypsin, subtilopeptidase A) and the alpha-macroglobulins of plasma are rapidly and selectively taken up by rabbit alveolar macrophages. The uptake occurs over a narrow zone of pH. Kinetics of the uptake is affected by temperature; in particular, incubation of macrophages at 37 degrees C before the addition of the labelled complex reduces the capacity to take up complexes. EDTA prevents the association of labelled complexes with macrophages, and can dissociate previously bound label. The effect of EDTA is reversed by the addition of calcium or magnesium or both. Iodoacetamide does not prevent the uptake of complexes but causes them to remain available for dissociation from the cells by EDTA. Incubation of complexes with macrophages at 37 degrees C with no iodoacetamide results in the appearance of trichloroacetic acid soluble products of the enzyme in the supernatant fluid. These observations indicate that the selective uptake of proteinase-alpha-macroglubin complexes by rabbit alveolar macrophages can be resolved into three phases: (1) membrane binding which depends upon divalent cations and is pH sensitive, (2) endocytosis inhibitable by iodoacetamide and (3) temperature-dependent hydrolysis of the contained labelled enzyme.