REGULATION OF ALPHA-1 PROTEINASE-INHIBITOR FUNCTION BY RABBIT ALVEOLAR MACROPHAGES - EVIDENCE FOR PROTEOLYTIC RATHER THAN OXIDATIVE INACTIVATION

Rabbit alveolar macrophages were cultured in an environment conducive to the secretion of both reactive O2 and proteinases, so that the relative importance of proteolytic and oxidative inactivation of .alpha.1-proteinase inhibitor by alveolar macrophages could be evaluated. The inactivation of .alpha.1-proteinase inhibitor was proportional to its proteolysis, and there was no detectable inactivation in the absence of proteolysis. Although the live macrophages were capable of secreting reactive O2, they did not inactivate .alpha.1-proteinase inhibitor by oxidation. The inactivation of .alpha.1-proteinase inhibitor by proteolysis was proportional to the secretion of elastinolytic activity by the alveolar macrophages. The inability of the alveolar macrophages to oxidize .alpha.1-proteinase inhibitor was attributed to the methionine in the macrophages, in secreted proteins, and in the culture medium competing for oxidants. Proteolytic inactivation of .alpha.1-proteinase inhibitor may be important in vivo and that the methionine concentration in vivo may protect .alpha.1-proteinase inhibitor from significant oxidative inactivation.