Differences in distribution and synthesis of the functional opponents alpha 1-proteinase inhibitor and neutrophil...

Alpha 1-proteinase inhibitor (alpha 1-Pi) is the main physiological inhibitor of neutrophil elastase, a serine protease that has been implicated in tissue degradation at inflammatory sites. We report here on an immunocytochemical study of various eukaryotic cells in order to show their content of alpha 1-Pi. The proteinase inhibitor is present in undifferentiated and differentiated HL-60 and U937 cells, in myeloblasts and neutrophils, and also in tissues such as liver, kidney, colon and eye where local inflammatory processes can take place. Labelling of HL-60, U937, neutrophils and HepG2 cells with [35S] methionine followed by immunoprecipitation of cell homogenates with an anti-alpha 1-Pi antibody revealed that these cells can synthesize alpha 1-Pi de novo, and secrete large amounts of the newly synthesized molecule into the medium. In contrast, neutrophil elastase is only present in white blood cells of myeloid and monocytic lineage but not in other tissues investigated which contain alpha 1-Pi. The results demonstrate the possibility of ubiquitous local synthesis of alpha 1-Pi ready to inhibit the elastase which is imported into the affected tissues during inflammatory processes by circulating cells of the haematopoietic system.