Human neutrophils express the α1-antitrypsin gene and produce α1-antitrypsin

R. M. Du Bois, J. F. Bernaudin, P. Paakko, R. Hubbard, H. Takahashi, V. Ferrans, R. G. Crystal

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Abstract

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 tissues from the destructive capacity of NE is provided by α1-antitrypsin (α1AT), 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 α1AT. Immunocytochemical analysis demonstrated that the neutrophil contains α1AT. Northern analysis and in situ hybridization with α1AT-specific probes demonstrated the presence of α1AT messenger RNA transcripts within neutrophils. [35S]methionine-labeling of neutrophils followed by immunoprecipitation of the supernatant with an anti-α1AT antibody and sodium dodecyl sulfate-acrylamide gel analysis demonstrated that neutrophils can synthesize α1AT de novo and secrete the synthesized molecule. In the presence of major neutrophil degranulation, the antiprotease effect of neutrophil α1AT is overwhelmed, allowing the NE to act unopposed in the extracellular microenvironment. However, in conditions where small amounts of NE are released by neutrophils, at least some of the secreted newly synthesized α1AT was capable of complexing with NE. Thus, despite the fact that the neutrophil cannot synthesize NE, it can synthesize and secrete α1AT, the inhibitor of NE, ie, the neutrophil is capable, to some extent, of modulating NE activity in the local milieu without the help of antiproteases produced by other cells.

Original languageEnglish
Pages (from-to)2724-2730
Number of pages7
JournalBlood
Volume77
Issue number12
Publication statusPublished - 1 Jan 1991

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Du Bois, R. M., Bernaudin, J. F., Paakko, P., Hubbard, R., Takahashi, H., Ferrans, V., & Crystal, R. G. (1991). Human neutrophils express the α1-antitrypsin gene and produce α1-antitrypsin. Blood, 77(12), 2724-2730.