Activated neutrophils secrete stored α1-antitrypsin

P. Paakko, M. Kirby, R. M. Du Bois, A. Gillissen, V. J. Ferrans, Ronald Crystal

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Neutrophil elastase (NE), a potent serine protease, is stored in primary granules of neutrophils and released following neutrophil activation. Alpha-1-antitrypsin (α1-AT), the major inhibitor of NE, is synthesized by mature neutrophils. In the context of the maintenance of tissue homeostasis, we hypothesized that neutrophils may be able to store α1-AT, thus having it available for release concordantly with NE. Immunofluorescence and quantitative flow-cytometric studies of neutrophils and monocytes labeled with fluorescein-conjugated α1-AT-antibody demonstrated larger amounts of cytoplasmic α1-AT in neutrophils than in monocytes. [35S]methionine-labeling and anti-α1-AT immunoprecipitation analysis showed that although both neutrophils and monocytes synthesize α1-AT, the proportion of newly synthesized intracellular α1-AT was much higher in neutrophils than in monocytes. Flow-cytometric analysis showed that in the presence of surface stimulation with cytochalasin B followed by formyl-methionyleucylphenylalanine (fMLP), mean intracellular α1-AT was decreased in stimulated neutrophils compared with that in resting cells, suggesting that the stored α1-AT was rapidly released following surface triggering. Evaluation of surface-stimulated neutrophils by [35S]methionine labeling and anti-α1-AT immunoprecipitation demonstrated increased secretion of α1-AT compared with that of resting neutrophils, with some of the secreted α1-AT capable of forming complexes with NE. Thus, neutrophils respond to surface stimulation not only by secreting NE but also by secreting its inhibitor, α1-AT, suggesting that these cells have an inherent mechanism for damping the local effects of NE, their most powerful proteolytic enzyme.

Original languageEnglish
Pages (from-to)1829-1833
Number of pages5
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume154
Issue number6
Publication statusPublished - 1 Dec 1996
Externally publishedYes

Fingerprint

Neutrophils
Leukocyte Elastase
Monocytes
Immunoprecipitation
Methionine
Secretory Proteinase Inhibitory Proteins
alpha 1-Antitrypsin
Neutrophil Activation
Cytochalasin B
Serine Proteases
Fluorescein
Fluorescent Antibody Technique
Homeostasis
Peptide Hydrolases
Maintenance
Antibodies

ASJC Scopus subject areas

  • Medicine(all)
  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Paakko, P., Kirby, M., Du Bois, R. M., Gillissen, A., Ferrans, V. J., & Crystal, R. (1996). Activated neutrophils secrete stored α1-antitrypsin. American Journal of Respiratory and Critical Care Medicine, 154(6), 1829-1833.

Activated neutrophils secrete stored α1-antitrypsin. / Paakko, P.; Kirby, M.; Du Bois, R. M.; Gillissen, A.; Ferrans, V. J.; Crystal, Ronald.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 154, No. 6, 01.12.1996, p. 1829-1833.

Research output: Contribution to journalArticle

Paakko, P, Kirby, M, Du Bois, RM, Gillissen, A, Ferrans, VJ & Crystal, R 1996, 'Activated neutrophils secrete stored α1-antitrypsin', American Journal of Respiratory and Critical Care Medicine, vol. 154, no. 6, pp. 1829-1833.
Paakko P, Kirby M, Du Bois RM, Gillissen A, Ferrans VJ, Crystal R. Activated neutrophils secrete stored α1-antitrypsin. American Journal of Respiratory and Critical Care Medicine. 1996 Dec 1;154(6):1829-1833.
Paakko, P. ; Kirby, M. ; Du Bois, R. M. ; Gillissen, A. ; Ferrans, V. J. ; Crystal, Ronald. / Activated neutrophils secrete stored α1-antitrypsin. In: American Journal of Respiratory and Critical Care Medicine. 1996 ; Vol. 154, No. 6. pp. 1829-1833.
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