Synthesis of alpha₁-protease inhibitor by resident and activated mouse alveolar macrophages

Alpha₁-protease inhibitor (α₁Pi), an acute-phase reactant, is the major inhibitor of neutral proteases causing lung tissue injury, such as elastase. While examining the acute-phase reaction to the nematode parasite Nippostrongylus brasiliensis, we noticed that the alveolar macrophage was closely associated with α₁Pi when the larvae were present in the lung. Histologic examination revealed marked edema and hemorrhage with numerous alveolar macrophages that stain intensely for intracellular α₁Pi. Isolation of these cells by bronchoalveolar lavage showed the macrophage to be activated. Cultured alveolar macrophages from normal and infected animals synthesized and secreted α₁Pi, as revealed by [³⁵S]-methionine incorporation, but the amounts were insignificant compared with that synthesized by hepatocytes. There was, however, no apparent difference in α₁Pi synthetic activity between normal and activated macrophages. The presence of demonstrable intracellular α₁Pi in the parasite-activated alveolar macrophage likely represents endocytosis as host protease- and/or parasite protease-antiprotease complexes. Although α₁Pi is synthesized primarily by hepatocytes, synthesis by alveolar macrophages may provide immediate local protection in the microenvironment of the lung during an acute inflammatory response.