Different distributions of kinetically apparent molecular varieties of alpha 2-macroglobulin in health and in patients with cryptogenic fibrosing alveolitis.

1. Proteinase inhibitors have been studied in whole serum by using a kinetic method that avoids potentially damaging protein separation procedures. 2. The alpha 2-macroglobulin of an individual can be allocated unambiguously into one of seven categories according to the binding of trypsin to inhibitor in two kinetically apparent binding modes (beta- and alpha-modes). 3. The distribution of alpha 2-macroglobulin beta:alpha ratios in a healthy adult population is defined, and shown to be independent of sex and age. 4. The distribution of beta:alpha ratios in a group of patients with cryptogenic fibrosing alveolitis was found to be significantly different (P less than 0.005) from the normal distribution. 5. Changes in the beta:alpha ratio were noted in five of six patients with cryptogenic fibrosing alveolitis after treatment, but on no occasion when two healthy subjects were assessed a total of nine times. 6. The molecular interpretation and the possible importance of altered proteinase inhibition in inflammation and fibrosis are discussed.