Bioactive cytidine deaminase, an inhibitor of granulocyte-macrophage colony-forming cells, is massively released in fulminant meningococcal sepsis

Roberto Benelli, Andrea Barbero, Silvano Ferrini, Patrizia Scapini, Marco Cassatella, Federico Bussolino, Carlo Tacchetti, Douglas M. Noonan, Adriana Albini

Research output: Contribution to journalArticle

Abstract

The extracellular activities of the human immunodeficiency virus (HIV) transactivator protein (Tat) include induction of angiogenesis and stimulation of monocyte migration. Here it is shown that polymorphonuclear leukocytes (PMNL), mostly neutrophils, rapidly invade in response to Tat in vivo and initiate the formation of new vessels. In vitro, Tat was chemotactic for PMNL and induced calcium (Ca2+) mobilization. Tat proteins with inactivating substitutions in the arginine-glycine-aspartic acid or basic domain were still active in inducing PMNL migration, whereas Tat peptides mapped the migration and Ca2+ mobilization activity to a cysteine-rich core domain, previously described as a Tat 'chemokine-like' region (peptide CysL24-51). Tat and the CysL24-51 peptide also induced PMNL superoxide production and the release of the angiogenic factors interleukin-8 and vascular endothelial growth factor from PMNL. CysL24-51 did not induce endothelial cell migration but was angiogenic in vivo. These data indicate that the Tat activity on PMNL is mediated by its chemokine-like region and that PMNL recruitment by Tat is linked to angiogenesis.

Original languageEnglish
Pages (from-to)1784-1787
Number of pages4
JournalJournal of Infectious Diseases
Volume182
Issue number6
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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