ALPHA-1-ANTITRYPSIN AND PROTEASE COMPLEXATION IS INDUCED BY LIPOPOLYSACCHARIDE, INTERLEUKIN-1-BETA, AND TUMOR-NECROSIS-FACTOR-ALPHA IN MONOCYTES

Local regulation of alpha 1-antitrypsin (alpha 1-AT) may have importan ce in maintenance of the protease-antiprotease balance in the microenv ironment of inflammatory cells. We therefore studied whether lipopolys accharide (LPS), interleukin-1 beta (IL-1 beta), and tumor necrosis fa ctor-alpha (TNF alpha) affect the pericellular concentration of alpha 1-AT in human peripheral blood mononuclear cells (PBMC). PBMC taken fr om normal healthy volunteers were treated with LPS, IL-1 beta, and TNF alpha, and the concentration of human alpha 1-AT in conditioned super natants was measured. When compared with unstimulated control supernat ants (147 +/- 19 ng/ml), LPS (439 +/- 66 ng/ml; p less than or equal t o 0.001), IL-1 beta (263 +/- 37 ng/ml; p less than or equal to 0.01), and TNF alpha (316 +/- 59 ng/ml; p less than or equal to 0.05) induced a 2- to 3-fold increase of alpha 1-AT. Up-regulation of alpha 1-AT pr otein correlated with an increase in alpha 1-AT mRNA, suggesting a sim ultaneous increase in alpha 1-AT synthesis. Despite the increase in al pha 1-AT concentration, functional antiprotease activity could not be detected. Furthermore, protease activity was present in all samples, w ith the amount of activity being inversely related to the amount of al pha 1-AT measured in supernatants. These findings suggest that local i nflammatory conditions up-regulate alpha 1-AT production by monocytes which complex with a protease derived from the PBMC population.