Alpha 1-antitrypsin and protease complexation is induced by lipopolysaccharide, interleukin-1β, and tumor necrosis factor-α in monocytes

Local regulation of α1-antitrypsin (α1-AT) may have importance in maintenance of the protease-anti-protease balance in the microenvironment of inflammatory cells. We therefore studied whether lipopolysaccharide (LPS), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNFα) affect the pericellular concentration of α1-AT in human peripheral blood mononuclear cells (PBMC). PBMC taken from normal healthy volunteers were treated with LPS, IL-1β, and TNFα, and the concentration of human α1-AT in conditioned supernatants was measured. When compared with unstimulated control supernatants (147 ± 19 ng/ml), LPS (439 ± 66 ng/ml; p ≤ 0.001), IL-1β (263 ± 37 ng/ml; p ≤ 0.01), and TNFα (316 ± 59 ng/ml; p ≤ 0.05) induced a 2- to 3-fold increase of α1-AT. Up-regulation of α1-AT protein correlated with an increase in α1-AT mRNA, suggesting a simultaneous increase in α1- AT synthesis. Despite the increase in α1-AT concentration, functional antiprotease activity could not be detected. Furthermore, protease activity was present in all samples, with the amount of activity being inversely related to the amount of α1-AT measured in supernatants. These findings suggest that local inflammatory conditions up-regulate α1-AT production by monocytes which complex with a protease derived from the PBMC population.