TY - JOUR
T1 - Bioactive cytidine deaminase, an inhibitor of granulocyte-macrophage colony-forming cells, is massively released in fulminant meningococcal sepsis
AU - Benelli, Roberto
AU - Barbero, Andrea
AU - Ferrini, Silvano
AU - Scapini, Patrizia
AU - Cassatella, Marco
AU - Bussolino, Federico
AU - Tacchetti, Carlo
AU - Noonan, Douglas M.
AU - Albini, Adriana
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1086/317596
DO - 10.1086/317596
M3 - Article
C2 - 11069255
AN - SCOPUS:0033680721
VL - 182
SP - 1784
EP - 1787
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 6
ER -