Human Neutrophils Express the al - Antitrypsin Gene and Produce al - An ti trypsin

The potent serine protease, neutrophil elastase (NE), is stored in neutrophil azurophilic granules, where it is available to degrade phagocytosed material and can be released by the cell to assist in tissue migration and help clear tissue debris. While neutrophils carry NE, they cannot produce it; the NE gene is expressed only in bone marrow granulocyte precursor cells. Protection of normal tissuesfrom the destructive capacity of NE is provided by al-antitrypsin (alAT), a 52-Kd serine antiprotease produced by hepatocytes and mononuclear phagocytes. In the context of the broad destructive capacity of NE, we evaluated the concept that human neutrophils may be able to modulate the extracellular activity of NE by synthesizing and secreting alAT. Immunocytochemical analysis demonstrated that the neutrophil contains a1 AT. Northern analysis and in situ hybridization with a1 AT-specific probes demonstrated the presence of a1 AT messenger RNA transcripts within neutrophils. [35S]methio-