Changes in serum and exudate levels of functional macroglobulins and anti-inflammatory effect of alpha 2-acute-phase macroglobulin on carrageenin-induced inflammation in rats.

Serum and exudate levels of functional macroglobulins that have the ability to inhibit proteinases were determined at various times after carrageenin injection into a preformed air-pouch on the back of rats. The trypsin-inhibiting activity of serum macroglobulins increased after a lag period of 3 hr, reached a maximum at 24 hr, and decreased steadily until day 16 after carrageenin injection. This change was in good agreement with the change in the serum level of alpha 2-acute-phase macroglobulin. In contrast with the serum level, the exudate level of functional macroglobulins was negligible on day 1, detectable on day 3, and remained at almost the same level from day 5 to day 16 after carregeenin injection. Macroglobulins were partially purified from rat serum obtained at 20 hr after carregeenin injection, and their anti-inflammatory activity was studied. The partially purified alpha 2-acute-phase macroglobulin and the alpha 1 macroglobulin were injected into the air-pouch immediately after carrageenin injection, with the result that a single injection of the functionally active alpha 2-acute-phase macroglobulin significantly inhibited the formation of granulation tissue on day 4 after the carrageenin injection, whereas functionally inactive alpha 1 macroglobulin was without effect. These results suggest that the inhibitory activity of macroglobulins on the development of granulation tissue is due to the proteinase-inhibiting capacity of macroglobulins.