Increased Catabolism of α-Macroglobulins after Intravenous Infusion of Trypsin-α1-Antitrypsin Complexes in Dogs

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Abstract
Double labeled trypsin-.alpha.1-antitrypsin complexes were formed in vitro and infused i.v. into dogs to study the interaction with .alpha.1-and .alpha.2-macroglobulin, the biological reaction and the rate of disappearance from plasma of the complex constituents. The amount of bound trypsin injected was varied from below to slightly above the trypsin-binding capacity of the dogs'' intravascular .alpha.-macroglobulin pool. More than half of the trypsin molecules were taken up by .alpha.-macroglobulins during the 1st h. The .alpha.-macroglobulins became saturated with trypsin during the 2nd h in 2 of the dogs. These subsequently went into shock, while the blood pressure remained stable during the 2nd critical h in animals with part of the .alpha.-macroglobulin free. A fast decrease in the plasma level of .alpha.-macroglobulins was regularly observed during the 1st 3 h after the injection of the trypsin-antitrypsin complexes. The results strongly suggested that the major elimination form of injected trypsin was trypsin-.alpha.-macroglobulin complexes. The plasma .alpha.-macroglobulin level was normalized after 1 wk, followed by some overshoot in the concentration the next week. The .alpha.1-antitrypsin molecules which had interacted with trypsin disappeared from plasma about twice as fast as native .alpha.1-antitrypsin. Availability of .alpha.-macroglobulins is apparently of vital importance for protection against trypsin; .alpha.1-antitrypsin probably has only a supporting carrier function.