Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Alpha-1-antitrypsin is produced by human neutrophil granulocytes and their precursors and liberated during granule exocytosis

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Reference values for the EORTC QLQ-C30 in patients with advanced stage Hodgkin Lymphoma and in Hodgkin Lymphoma survivors

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Vitamin E and acute graft-versus-host disease after myeloablative allogeneic hematopoietic cell transplantation

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Transient congenital hyperinsulinism and hemolytic disease of a newborn despite rhesus D prophylaxis: a case report

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Acute liver failure in a four-year old girl during maintenance therapy of acute lymphoblastic leukemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Kongenitte portosystemiske shunter, diagnose og behandling af en multisystemisk sygdom hos børn

    Research output: Contribution to journalReviewResearchpeer-review

View graph of relations
Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3. Transcription profiling data suggest that A1AT is expressed by human neutrophil granulocytes during all developmental stages. A1AT has hitherto only been found associated with azurophile granules in neutrophils indicative of A1AT expression being restricted to the promyelocyte stage. We examined the localization and production of A1AT in healthy donor neutrophils and found A1AT to be a constituent of all granule subtypes and to be released from neutrophils following stimulation. A1AT is produced at all stages of myeloid maturation in the bone marrow. The production increases as neutrophils enter circulation and increases further upon migration to tissues as observed in skin windows and when blood neutrophils are incubated with granulocyte colony-stimulating factor. Neutrophils from patients with A1AT-deficiency carrying the (PI)ZZ mutation in the A1AT gene appeared structurally and functionally normal, but A1AT produced in leukocytes of these patients lacked the ability to bind proteases efficiently. We conclude that A1AT generation and release from neutrophils add significantly to the antiprotease levels in tissues during inflammation. Impaired binding of neutrophil A1AT to serine proteases in patients with (PI)ZZ mutations may enhance their susceptibility to the development of emphysema.
Original languageEnglish
JournalEuropean Journal of Haematology
Volume86
Issue number6
Pages (from-to)517-30
Number of pages14
ISSN0902-4441
DOIs
Publication statusPublished - 1 Jun 2011

    Research areas

  • Case-Control Studies, Cell Degranulation, Cell Differentiation, Cytoplasmic Granules, Eosinophils, Exocytosis, Genotype, Granulocyte Colony Stimulating Factor, Recombinant, Humans, Liver Transplantation, Lung Transplantation, Microscopy, Electron, Transmission, Mutation, Neutrophils, RNA, Messenger, Skin Window Technique, alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency

ID: 32701825